WO1995003036A1 - Anti-angiogenic compositions and methods of use - Google Patents

Anti-angiogenic compositions and methods of use Download PDF

Info

Publication number
WO1995003036A1
WO1995003036A1 PCT/CA1994/000373 CA9400373W WO9503036A1 WO 1995003036 A1 WO1995003036 A1 WO 1995003036A1 CA 9400373 W CA9400373 W CA 9400373W WO 9503036 A1 WO9503036 A1 WO 9503036A1
Authority
WO
WIPO (PCT)
Prior art keywords
taxol
stent
composition
microspheres
tumor
Prior art date
Application number
PCT/CA1994/000373
Other languages
English (en)
French (fr)
Inventor
Helen M. Burt
William L. Hunter
Lindsay S. Machan
A. Larry Arsenault
John K. Jackson
Original Assignee
Angiogenesis Technologies, Inc.
The University Of British Columbia
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=22245764&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=WO1995003036(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Priority to CA002167268A priority Critical patent/CA2167268C/en
Priority to EP94920360A priority patent/EP0706376B2/en
Priority to DE69403966T priority patent/DE69403966T3/de
Priority to JP50482395A priority patent/JP3423317B2/ja
Priority to DK94920360T priority patent/DK0706376T4/da
Priority to AU71192/94A priority patent/AU693797B2/en
Priority to KR1020117007294A priority patent/KR101222904B1/ko
Priority to NZ268326A priority patent/NZ268326A/en
Priority to DK01117873T priority patent/DK1159974T3/da
Application filed by Angiogenesis Technologies, Inc., The University Of British Columbia filed Critical Angiogenesis Technologies, Inc.
Publication of WO1995003036A1 publication Critical patent/WO1995003036A1/en
Priority to US08/486,867 priority patent/US20030203976A1/en
Priority to US08/478,203 priority patent/US5716981A/en
Priority to US08/478,914 priority patent/US5994341A/en
Priority to US08/472,413 priority patent/US5886026A/en
Priority to NO19960226A priority patent/NO324275B1/no
Priority to GR970402471T priority patent/GR3024833T3/el
Priority to US08/984,258 priority patent/US20020165265A1/en
Priority to US09/294,458 priority patent/US6506411B2/en
Priority to US09/925,220 priority patent/US6544544B2/en
Priority to US09/927,882 priority patent/US20020119202A1/en
Priority to US10/112,921 priority patent/US6846841B2/en
Priority to US10/389,262 priority patent/US20040076672A1/en
Priority to US10/390,534 priority patent/US20040062810A1/en
Priority to US10/959,349 priority patent/US7820193B2/en
Priority to US10/959,398 priority patent/US20050208137A1/en
Priority to US10/962,578 priority patent/US20050042295A1/en
Priority to US11/151,399 priority patent/US20060127445A1/en
Priority to US11/207,021 priority patent/US20060035831A1/en
Priority to US11/206,993 priority patent/US20060035830A1/en
Priority to US11/206,779 priority patent/US20060034932A1/en
Priority to US11/207,058 priority patent/US20060035832A1/en
Priority to US11/207,059 priority patent/US20060035833A1/en
Priority to US11/332,170 priority patent/US20060121117A1/en
Priority to US11/435,854 priority patent/US20070003630A1/en
Priority to US11/435,780 priority patent/US20070003629A1/en
Priority to US11/435,742 priority patent/US20060240113A1/en
Priority to NO20073066A priority patent/NO20073066L/no
Priority to US11/830,080 priority patent/US20070298123A1/en
Priority to US11/830,186 priority patent/US20080020063A1/en
Priority to US11/830,208 priority patent/US20090074830A1/en
Priority to US11/830,240 priority patent/US20080166387A1/en
Priority to US12/098,173 priority patent/US20090036517A1/en
Priority to US12/817,682 priority patent/US20110071612A1/en
Priority to US12/820,523 priority patent/US20110066251A1/en
Priority to US12/820,614 priority patent/US20110118825A1/en

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/24—Heavy metals; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/12—Ketones
    • A61K31/122—Ketones having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/13—Amines
    • A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
    • A61K31/136—Amines having aromatic rings, e.g. ketamine, nortriptyline having the amino group directly attached to the aromatic ring, e.g. benzeneamine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
    • A61K31/203—Retinoic acids ; Salts thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/337—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/425—Thiazoles
    • A61K31/426—1,3-Thiazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/425—Thiazoles
    • A61K31/427—Thiazoles not condensed and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/4745—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A61K31/525—Isoalloxazines, e.g. riboflavins, vitamin B2
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/555—Heterocyclic compounds containing heavy metals, e.g. hemin, hematin, melarsoprol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/702—Oligosaccharides, i.e. having three to five saccharide radicals attached to each other by glycosidic linkages
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/24—Heavy metals; Compounds thereof
    • A61K33/30—Zinc; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/55—Protease inhibitors
    • A61K38/57—Protease inhibitors from animals; from humans
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0048—Eye, e.g. artificial tears
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0048—Eye, e.g. artificial tears
    • A61K9/0051—Ocular inserts, ocular implants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1629—Organic macromolecular compounds
    • A61K9/1635—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1629—Organic macromolecular compounds
    • A61K9/1641—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poloxamers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1629—Organic macromolecular compounds
    • A61K9/1641—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poloxamers
    • A61K9/1647—Polyesters, e.g. poly(lactide-co-glycolide)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1629—Organic macromolecular compounds
    • A61K9/1658—Proteins, e.g. albumin, gelatin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5005—Wall or coating material
    • A61K9/5021—Organic macromolecular compounds
    • A61K9/5031—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poly(lactide-co-glycolide)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/51—Nanocapsules; Nanoparticles
    • A61K9/5107—Excipients; Inactive ingredients
    • A61K9/513—Organic macromolecular compounds; Dendrimers
    • A61K9/5146—Organic macromolecular compounds; Dendrimers obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyamines, polyanhydrides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/51—Nanocapsules; Nanoparticles
    • A61K9/5107—Excipients; Inactive ingredients
    • A61K9/513—Organic macromolecular compounds; Dendrimers
    • A61K9/5146—Organic macromolecular compounds; Dendrimers obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyamines, polyanhydrides
    • A61K9/5153—Polyesters, e.g. poly(lactide-co-glycolide)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • A61K9/7007—Drug-containing films, membranes or sheets
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/08—Materials for coatings
    • A61L31/10—Macromolecular materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L31/145—Hydrogels or hydrocolloids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L31/16—Biologically active materials, e.g. therapeutic substances
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/14—Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C233/00—Carboxylic acid amides
    • C07C233/64—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/81—Protease inhibitors
    • C07K14/8107—Endopeptidase (E.C. 3.4.21-99) inhibitors
    • C07K14/811—Serine protease (E.C. 3.4.21) inhibitors
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L23/00—Compositions of homopolymers or copolymers of unsaturated aliphatic hydrocarbons having only one carbon-to-carbon double bond; Compositions of derivatives of such polymers
    • C08L23/02—Compositions of homopolymers or copolymers of unsaturated aliphatic hydrocarbons having only one carbon-to-carbon double bond; Compositions of derivatives of such polymers not modified by chemical after-treatment
    • C08L23/04—Homopolymers or copolymers of ethene
    • C08L23/08—Copolymers of ethene
    • C08L23/0846—Copolymers of ethene with unsaturated hydrocarbons containing other atoms than carbon or hydrogen atoms
    • C08L23/0853—Vinylacetate
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L67/00—Compositions of polyesters obtained by reactions forming a carboxylic ester link in the main chain; Compositions of derivatives of such polymers
    • C08L67/04—Polyesters derived from hydroxycarboxylic acids, e.g. lactones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/416—Anti-neoplastic or anti-proliferative or anti-restenosis or anti-angiogenic agents, e.g. paclitaxel, sirolimus
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
    • A61L2300/606—Coatings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
    • A61L2300/62—Encapsulated active agents, e.g. emulsified droplets
    • A61L2300/622—Microcapsules
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2430/00—Materials or treatment for tissue regeneration
    • A61L2430/36—Materials or treatment for tissue regeneration for embolization or occlusion, e.g. vaso-occlusive compositions or devices
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L2203/00—Applications
    • C08L2203/02—Applications for biomedical use
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L2312/00—Crosslinking
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L29/00—Compositions of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by an alcohol, ether, aldehydo, ketonic, acetal or ketal radical; Compositions of hydrolysed polymers of esters of unsaturated alcohols with saturated carboxylic acids; Compositions of derivatives of such polymers
    • C08L29/02—Homopolymers or copolymers of unsaturated alcohols
    • C08L29/04—Polyvinyl alcohol; Partially hydrolysed homopolymers or copolymers of esters of unsaturated alcohols with saturated carboxylic acids
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S977/00—Nanotechnology
    • Y10S977/70—Nanostructure
    • Y10S977/773—Nanoparticle, i.e. structure having three dimensions of 100 nm or less
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S977/00—Nanotechnology
    • Y10S977/902—Specified use of nanostructure
    • Y10S977/904—Specified use of nanostructure for medical, immunological, body treatment, or diagnosis
    • Y10S977/915—Therapeutic or pharmaceutical composition

Definitions

  • stents comprising a generally tubular structure, the surface being coated with one or more anti-angiogenic compositions.
  • methods are provided for expanding the lumen of a body passageway, comprising inserting a stent into the passageway, the stent having a generally tubular structure, the surface of the structure being coated with an anti- angiogenic composition as described above, such that the passageway is expanded.
  • methods for treating tumor excision sites comprising administering an anti- angiogenic composition as described above to the resection margins of a tumor subsequent to excision, such that the local recurrence of cancer and the formation of new blood vessels at the site is inhibited.
  • methods for treating corneal neovascularization comprising the step of administering a therapeuticaUy effective amount of an anti-angiogenic composition as described above to the cornea, such that the formation of blood vessels is inhibited.
  • the anti-angiogenic composition further comprises a topical corticosteroid.
  • methods are provided for inhibiting angiogenesis in patients with non-tumorigenic, angiogenesis-dependent diseases, comprising administering a therapeuticaUy effective amount of a composition comprising taxol to a patient with a non- tumorigenic angiogenesis-dependent disease, such that the formation of new blood vessels is inhibited.
  • methods are provided for embolizing blood vessels in non-tumorigenic, angiogenesis-dependent diseases, comprising delivering to the vessel a therapeuticaUy effective amount of a composition comprising taxol, such that the blood vessel is effectively occluded.
  • methods are provided for treating a tumor excision site, comprising administering a composition comprising taxol to the resection margin of a tumor subsequent t,o excision, such that the local recurrence of cancer and the formation of new blood vessels at the site is inhibited.
  • methods are provided for treating ' corneal neovascularization, comprising administering a therapeuticaUy effective amount of a composition comprising taxol to the cornea, such that the formation of new vessels is inhibited.
  • pharmaceutical products comprising (a) taxol, in a container, and (b) a notice associated with the container in form prescribed by a governmental agency regulating the manufacture, use, or sale of pharmaceuticals, which notice is reflective of approval by the agency of the taxol, for human or veterinary administration to treat non-tumorigenic angiogenesis-dependent diseases.
  • a governmental agency regulating the manufacture, use, or sale of pharmaceuticals
  • Federal Law requires that the use of a pharmaceutical agent in the therapy of humans be approved by an agency of the Federal government.
  • responsibility for enforcement in the United States is with the Food and Drug Administration, which issues appropriate regulations for securing such approval, detailed in 21 U.S.C. ⁇ 301-392.
  • Figure 1A is a photograph which shows a shell-less egg culture on day 6.
  • Figure IB is a digitized computer-displayed image taken with a stereomicroscope of living, unstained capillaries (1040x).
  • Figure IC is a corrosion casting which shows CAM microvasculature that are fed by larger, underlying vessels (arrows; 1300x).
  • Figure ID depicts a 0.5 mm thick plastic section cut t isversely through the CAM, and recorded at the light microscope level.
  • This pi-otograph shows the composition of the CAM, including an outer double-layered ectoderm (Ec), a mesoderm (M) containing capillaries (arrows) and scattered adventitila cells, and a single layered endoderm (En) (400x).
  • Ec outer double-layered ectoderm
  • M mesoderm
  • End single layered endoderm
  • Figure IE is a photograph at the electron microscope level (3500x) wherein typical capillary structure is presented showing thin-walled endothelial cells, (arrowheads) and an associated pericyte.
  • Figures 2A, 2B, 2C and 2D are a series of digitized images of four different, unstained CAMs taken after a 48 hour exposure to taxol.
  • Figures 3A, 3B and 3C are a series of photographs of 0.5 mm thick plastic sections transversely cut through a taxol-treated CAM at three different locations within the avascular zone.
  • Figures 4A, 4B and 4C are series of electron micrographs which were taken from locations similar to that of Figures 3A, 3B and 3C (respectively) above.
  • Figure 5 is a bar graph which depicts the size distribution of microspheres by number (5% ELVAX with 10 mg sodium suramin into 5% PVA).
  • Figure 6 is a bar graph which depicts the size distribution of microspheres by weight (5% ELVAX with 10 mg sodium suramin into 5% PVA).
  • Figure 10 is a bar graph which depicts the size distribution by weight of 5% PLL microspheres containing 10 mg sodium suramin made in 5% PVA containing 10% NaCl.
  • Figure 13 is an illustration of a representative embodiment of hepatic tumor embolization.
  • Figure 15A is a graph which shows the effect of the EVA.PLA polymer blend ratio upon aggregation of microspheres.
  • Figure 15B is a scanning electron micrograph which shows the size of "small” microspheres.
  • Figure 15C is a scanning electron micrograph which shows the size of "large” microspheres.
  • Figure 15D is a graph which depicts the time course of in vitro taxol release from 0.6% w/v taxol-loaded 50:50 EVA:PLA polymer blend microspheres into phosphate buffered saline (pH 7.4) at 37°C. Open circles are "small” sized microspheres, and closed circles are "large” sized microspheres.
  • Figure 15E is a photograph of a CAM which shows the results of taxol release by microspheres ("MS").
  • Figure 15F is a photograph similar to that of 15E at increased magnification.
  • Figure 16 is a graph which shows release rate profiles from polycaprolactone microspheres containing 1%, 2%, 5% or 10% taxol into phosphate buffered saline at 37°C.
  • Figure 16B is a photograph which shows a CAM treated with control microspheres.
  • Figure 16C is a photograph which shows a CAM treated with 5% taxol loaded microspheres.
  • Figures 17A and 17B are two graphs which show the release of taxol from EVA films, and the percent taxol remaining in those same films over time.
  • Figure 17C is a graph which shows the swelling of EVA/F127 films with no taxol over time.
  • Figure 17D is a graph which shows the swelling of EVA/Span 80 films with no taxol over time.
  • Figure 17E is a graph which depicts a stress vs. strain curve for various EVA/F127 blends.
  • Figures 18F and 18G are graphs which depict the effect of varying quantities of taxol on the total amount of taxol released from a 20%MePEG/PCL blend.
  • Figure 18H is a graph which depicts the effect of MePEG on the tensile strength of a MePEG/PCL polymer.
  • Figure 22A is a photograph of synovium from a PBS injected joint.
  • Figure 22B is a photograph of synovium from a microsphere injected joint.
  • Figure 22C is a photograph of cartilage from joints injected with PBS, and
  • Figure 22D is a photograph of cartilage from joints injected with microspheres.
  • inhibition of vascular growth by the sample to be tested may be readily determined by visualization of the chick chorioallantoic membrane in the region surrounding the methyl cellulose disk. Inhibition of vascular growth may also be determined quantitatively, for example, by determining the number and size of blood vessels surrounding the methyl cellulose disk, as compared to a control methyl cellulose disk. Particularly preferred anti-angiogenic factors suitable for use within the present invention completely inhibit the formation of new blood vessels in the assay described above.
  • assays may also be utilized to determine the efficacy of anti-angiogenic factors in vivo, including for example, mouse models which have been developed for this purpose (see Roberston et al., Cancer. Res. 52:1339-1344, 1991).
  • mouse models which have been developed for this purpose (see Roberston et al., Cancer. Res. 52:1339-1344, 1991).
  • representative in vivo assays relating to various aspects of the inventions described herein have been described in more detail below in Examples 5 to 7, and 17 to 19.
  • compositions comprising an anti-angiogenic factor and a polymeric carrier.
  • anti-angiogenic factors may be readily utilized within the context of the present invention. Representative examples include Anti-Invasive Factor, retinoic acid and derivatives thereof, taxol, and members of the group consisting of Suramin, Tissue Inhibitor of Metalloproteinase-1, Tissue Inhibitor of Metalloproteinase-2, Plasminogen Activator Inhibitor- 1 and Plasminogen Activator Inhibitor-2. These and other anti-angiogenic factors will be discussed in more detail below.
  • AIF suitable for use within the present invention may be readily prepared utilizing techniques known in the art (e.g., Eisentein et al, supra; Kuettner and Pauli, supra; and Langer et al., supra). Purified constituents of AIF such as Cartilage-Derived Inhibitor ("CDI") (see Moses et al., Science 2 S: 1408-1410, 1990) may also be readily prepared and utilized within the context of the present invention.
  • CDI Cartilage-Derived Inhibitor
  • Suramin is a polysulfonated naphthylurea compound that is typically used as a trypanocidal agent. Briefly, Suramin blocks the specific cell surface binding of various growth factors such as platelet derived growth factor (“PDGF”), epidermal growth factor (“EGF”), transforming growth factor (“TGF- ⁇ ”), insulin-like growth factor (“IGF-1”) and fibroblast growth factor (“ ⁇ FGF”).
  • PDGF platelet derived growth factor
  • EGF- ⁇ epidermal growth factor
  • TGF- ⁇ transforming growth factor
  • IGF-1 insulin-like growth factor
  • ⁇ FGF fibroblast growth factor
  • Suramin may be prepared in accordance with known techniques, or readily obtained from a variety of commercial sources, including for example Mobay Chemical Co., New York, (see Gagliardi et al., Cancer Res. 52:5073-5075, 1992; and Coffey, Jr., et al., 7. of Cell. Phys. 252:143-148, 1987
  • PAI-2 is a 56 kDa protein which is secreted by monocytes and macrophages. It is believed to regulate fibrinolytic activity, and in particular inhibits urokinase plasminogen activator and tissue plasminogen activator, thereby preventing fibrinolysis.
  • a wide variety of other anti-angiogenic factors may also be utilized within the context of the present invention. Representative examples include Platelet Factor 4 (Sigma Chemical Co., #F1385); Protamine Sulphate (Clupeine) (Sigma Chemical Co., #P4505); Sulphated Chitin Derivatives (prepared from queen crab shells), (Sigma Chemical Co., #C3641; Murata et al., Cancer Res.
  • Anti-angiogenic compositions of the present invention may additionally comprise a wide variety of compounds in addition to the anti- angiogenic factor and polymeric carrier.
  • anti-angiogenic compositions of the present invention may also, within certain embodiments of the invention, also comprise one or more antibiotics, anti-inflamatories, anti ⁇ viral agents, anti-fungal agents and/or anti-protozoal agents.
  • antibiotics included within the compositions described herein include: penicillins; cephalosporins such as cefadroxil, cefazolin, cefaclor; aminoglycosides such as gentamycin and tobramycin; sulfonamides such as sulfamethoxazole; and metronidazole.
  • anti- mflammatories include: steroids such as prednisone, prednisolone, hydrocortisone, adrenocorticotropic hormone, and sulfasalazine; and non- steroidal anti-inflammatory drugs ("NSAIDS") such as aspirin, ibuprofen, naproxen, fenoporfen, indomethacin, and phenylbutazone.
  • NSA non- steroidal anti-inflammatory drugs
  • antiviral agents include acyclovir, ganciclovir, zidovudine.
  • antifungal agents include: nystatin, ketoconazole, griseofulvin, flucytosine, miconazole, clotrimazole.
  • antiprotozoal agents include: pentamidine isethionate, quinine, chloroquine, and mefloquine.
  • Anti-angiogenic compositions of the present invention may also contain one or more hormones such as thyroid hormone, estrogen, progesterone, cortisone and/or growth hormone, other biologically active molecules such as insulin, as well as Tj-f i (e.g., Interleukins -2, -12, and -15, gamma interferon or Tj-j2 (e.g., Interleukins -4 and -10) cytokines.
  • hormones such as thyroid hormone, estrogen, progesterone, cortisone and/or growth hormone
  • other biologically active molecules such as insulin
  • Tj-f i e.g., Interleukins -2, -12, and -15
  • Tj-j2 e.g., Interleukins -4 and -10
  • Anti-angiogenic compositions of the present invention may also comprise additional ingredients such as surfactants (either hydrophilic or hydrophobic; see Example 13), anti-neoplastic or chemotherapeutic agents (e.g., 5-fluorouracil, vinblastine, doxyrubicin, adriamycin, or tamocifen), radioactive agents (e.g., Cu-64, Ga-67, Ga-68, Zr-89, Ru-97, Tc-99m, Rh-105, Pd-109, In- Ill, 1-123, 1-125, 1-131, Re-186, Re-188, Au-198, Au-199, Pb-203, At-211, Pb-212 and Bi-212) or toxins (e.g., ricin, abrin, diptheria toxin, cholera toxin, gelonin, pokeweed antiviral protein, tritin, Shigella toxin, and Pseudomonas exotoxin A).
  • anti-angiogenic compositions of the present invention comprise an anti-angiogenic factor and a polymeric carrier.
  • anti-angiogenic compositions of the present invention may include a wide variety of polymeric carriers, including for example both biodegradable and non-biodegradable compositions.
  • biodegradable compositions include albumin, gelatin, starch, cellulose, destrans, polysaccharides, fibrinogen, poly (d,l lactide), poly (d,l-lactide-co- glycolide), poly (glycolide), poly (hydroxybutyrate), poly (alkylcarbonate) and poly (orthoesters) (see generally, Ilium, L., Davids, S.S. (eds.) "Polymers in controlled Drug Delivery” Wright, Bristol, 1987; Arshady, J. Controlled Release 27:1-22, 1991; Pitt, Int. J. Phar. 59: 173-196, 1990; Holland et al., J. Controlled Release 4:155-0180, 1986).
  • nondegradable polymers include EVA copolymers, silicone rubber and poly (methylmethacrylate).
  • Particularly preferred polymeric carriers include EVA copolymer (e.g., ELVAX 40, poly(ethylene-vinyl acetate) crosslinked with 40% vinyl acetate; DuPont), poly(lactic-co-glycolic acid), polycaprolactone, polylactic acid, copolymers of poly(ethylene-vinyl acetate) crosslinked with 40% vinyl acetate and polylactic acid, and copolymers of polylactic acid and polycaprolactone.
  • EVA copolymer e.g., ELVAX 40, poly(ethylene-vinyl acetate) crosslinked with 40% vinyl acetate; DuPont
  • poly(lactic-co-glycolic acid) polycaprolactone
  • polylactic acid copolymers of poly(ethylene-vinyl acetate) crosslinked with 40% vinyl acetate and polylactic acid
  • copolymers of polylactic acid and polycaprolactone
  • Polymeric carriers may be fashioned in a variety of forms, including for example, as nanospheres or microspheres, rod-shaped devices, pellets, slabs, or capsules (see, e.g., Goodell et al., Am. J. Hosp. Pharm. 45:1454- 1461, 1986; Langer et al., "Controlled release of macromolecules from polymers", in Biomedical polymers, Polymeric materials and pharmaceuticals for biomedical use, Goldberg, E.P., Nakagim, A. (eds.) Academic Press, pp. 113-137, 1980; Rhine et al., J. Pharm. Sci. 69:265-270, 19S0; Brown et al., J. Pharm. Sci. 72:1181-1185, 1983; and Bawa et al., J. Controlled Release 2:259-267, 1985).
  • anti-angiogenic compositions may be fashioned in any size ranging from nanospheres to microspheres (e.g., from 0.1 ⁇ m to 500 ⁇ m), depending upon the particular use.
  • nanospheres e.g., from 0.1 ⁇ m to 500 ⁇ m
  • Such nanoparticles may also be readily applied as a "spray", which solidifies into a film or coating.
  • Nanoparticles may be prepared in a wide array of sizes, including for example, from 0.1 ⁇ m to 3 ⁇ m, from 10 ⁇ m to 30 ⁇ m, and from 30 ⁇ m to 100 ⁇ m (see Example 8).
  • Anti-angiogenic compositions may also be prepared, given e disclosure provided herein, for a variety of other applications.
  • the compositions of the present invention may be incorporated into polymers as nanoparticles (see generally, Kreuter J. Controlled Release 26:169-176, 1991; Couvreur and Vauthier, J. Controlled Release 27: 187-198, 1991).
  • Such nanoparticles may also be readily applied as a "spray", which solidifies into a film or coating.
  • Nanoparticles may be prepared in a wide array of sizes, including for example, from 0.1 ⁇ m to 3 ⁇ m, from 10 ⁇ m to 30 ⁇ m, and from 30 ⁇ m to 100 ⁇ m (see Example 8).
  • the anti-angiogenic compositions of the present invention may be formed as a film.
  • such films are generally less than 5, 4, 3, 2, or 1, mm thick, more preferably less than 0.75 mm or 0.5 mm thick, and most preferably less than 500 ⁇ m to 100 ⁇ m thick.
  • Such films are preferably flexible with a good tensile strength (e.g., greater than 50, preferably greater than 100, and more preferably greater than 150 or 200 N/cm 2 ), good adhesive properties (Le., readily adheres to moist or wet surfaces), and has controlled permeability. Representative examples of such films are set forth below in the Examples (see e.g., Example 13).
  • the present invention also provides a variety of methods which utilize the above-described anti-angiogenic compositions.
  • methods are provided for embolizing a blood vessel, comprising the step of delivering into the vessel a therapeuticaUy effective amount of an anti- angiogenic composition (as described above), such that the blood vessel js effectively occluded.
  • TherapeuticaUy effective amounts suitable for occluding blood vessels may be readily determined given the disclosure provided below, and as described in Example 6.
  • the anti-angiogenic composition is delivered to a blood vessel which nourishes a tumor (see Figure 13).
  • preoperative embolization may be employed hours or days before surgical resection in order to reduce operative blood loss, shorten the duration of the operation, and reduce the risk of dissemination of viable malignant cells by surgical manipulation of the tumor.
  • Many tumors may be successfully embolized preoperatively, including for example nasopharyngeal tumors, glomus jugular tumors, meningiomas, chemodectomas, and vagal neuromas.
  • Embolization therapy generally results in the distribution of compositions containing anti-angiogenic factors throughout the interstices of the tumor or vascular mass to be treated.
  • the physical bulk of the embolic particles clogging the arterial lumen results in the occlusion of the blood supply.
  • an anti-angiogenic factor(s) prevents the formation of new blood vessels to supply the tumor or vascular mass, enhancing the devitalizing effect of cutting off the blood supply.
  • tumors are typically divided into two classes: benign and malignant.
  • benign tumor the cells retain their differentiated features and do not divide in a completely uncontrolled manner.
  • the tumor is localized and nonmetastatic.
  • malignant tumor the cells become undifferentiated, do not respond to the body's growth and hormonal signals, and multiply in an uncontrolled manner; the tumor is invasive and capable of spreading to distant sites (metastasizing).
  • this will be a segmental branch of the hepatic artery, but it could be that the entire hepatic artery distal to the origin of the gastroduodenal artery, or even multiple separate arteries, will need to be blocked depending on the extent of tumor and its individual blood supply.
  • the artery is embolized by injecting anti-angiogenic compositions (as described above) through the arterial catheter until flow in the artery to be blocked ceases, preferably even after observation for 5 minutes. Occlusion of the artery may be confirmed by injecting radiopaque contrast through the catheter and demonstrating by fluoroscopy or X-ray film that the vessel which previously filled with contrast no longer does so. The same procedure may be repeated with each feeding artery to be occluded.
  • a secondary tumor, or metastasis is a tumor which originated elsewhere in the body but has now spread to a distant organ.
  • the common routes for metastasis are direct growth into adjacent structures, spread through the vascular or lymphatic systems, and tracking along tissue planes and body spaces (peritoneal fluid, cerebrospinal fluid, etc.).
  • Secondary hepatic tumors are one of the most common causes of death in cancer patients and are by far and away the most common form of liver tumor.
  • tumors which are most likely to spread to the liver include: cancer of the stomach, colon, and pancreas; melanoma; tumors of the lung, oropharynx, and bladder; Hodgkin's and non-Hodgkin's lymphoma; tumors of the breast, ovary, and prostate.
  • Each one of the above- named primary tumors has numerous different tumor types which may be treated by arterial embolization (for example, there are over 32 different types of ovarian cancer).
  • embolization may be accomplished in order to treat conditions of excessive bleeding.
  • menorrhagia excessive bleeding with menstruation
  • the uterine arteries are branches of the internal iliac arteries bilaterally.
  • a catheter may be inserted via the femoral or brachial artery, and advanced into each uterine artery by steering it through the arterial system under fluoroscopic guidance. The catheter should be advanced as far as necessary to allow complete blockage of the blood vessels to the uterus, while sparing as many arterial branches that arise from the uterine artery and supply normal structures as possible.
  • each artery on each side may be embolized, but occasionally multiple separate arteries may need to be blocked depending on the individual blood supply.
  • each artery may be embolized by administration of the anti-angiogenic compositions as described above.
  • arterial embolization may be accomplished in a variety of other conditions, including for example for acute bleeding, vascular abnormalities, central nervous system disorders, and hypersplenism.
  • stents comprising a generally tubular structure (which includes for example, spiral shapes), the surface of which is coated with a composition as described above.
  • a stent is a scaffolding, usually cylindrical in shape, that may be inserted into a body passageway (e.g., bile ducts), which has been narrowed by a disease process (e.g., ingrowth by a tumor) in order to prevent closure or reclosure of the passageway.
  • a body passageway e.g., bile ducts
  • a disease process e.g., ingrowth by a tumor
  • Stents may be readily obtained from commercial sources, or constructed in accordance with well known techniques.
  • Representative examples of stents include those described in U.S. Patent No. 4,776,337, entitled “Expandable Intraluminal Graft, and Method and Apparatus for Implanting and Expandable Intraluminal Graft", U.S. Patent No. 5,176,626, entitled “Indwelling Stent", U.S. Patent No. 5,147,370 entitled “Nitinol Stent for Hollow Body Conduits", U.S. Patent No. 5,064,435 entitled “Self-Expanding Prosthesis Having Stable Axial Length", U.S. Patent No. 5,052,998 entitled “Indwelling Stent and Method of Use", and U.S. Patent No.
  • Stents may be coated with anti-angiogenic compositions or anti- angiogenic factors of the present invention using a variety of methods, including for example: (a) by directly affixing to the stent an anti-angiogenic composition (e.g., by either spraying the stent with a polymer/drug film, or by dipping the stent into a polymer/drug solution), (b) by coating the stent with a substance such as a hydrogel which will in turn absorb the anti-angiogenic composition (or anti-angiogenic factor above), (c) by interweaving anti-angiogenic composition coated thread (or the polymer itself formed into a thread) into the stent structure, (d) by inserting the stent into a sleeve or mesh which is comprised of or coated with an anti-angiogenic composition, or (e) constructing the stent itself with an anti-angiogenic composition
  • stents are inserted in a similar fashion regardless of the site or the disease being treated.
  • a preinsertion examination usually a diagnostic imaging procedure, endoscopy, or direct visualization at the time of surgery, is generally first performed in order to determine the appropriate positioning for stent insertion.
  • a guidewire is then advanced through the lesion or proposed site of insertion, and over this is passed a delivery catheter which allows a stent in its collapsed form to be inserted.
  • stents are capable of being compressed, so that they can be inserted through tiny cavities via small catheters, and then expanded to a larger diameter once they are at the desired location. Once expanded, the stent physically forces the walls of the passageway apart and holds it open.
  • the stent may be self-expanding (e.g., the Wallstent and Gianturco stents), balloon expandable (e.g., the Palmaz stent and Strecker stent), or implanted by a change in temperature (e.g.. the Nitinol stent).
  • Stents are typically maneuvered into place under radiologic or direct visual control, taking particular care to place the stent precisely across the narrowing in the organ being treated.
  • the delivery catheter is then removed, leaving the stent standing on its own as a scaffold.
  • a post insertion examination usually an x-ray, is often utilized to confirm appropriate positioning.
  • methods for eliminating biliary obstructions, comprising inserting a biliary stent into a biliary passageway, the stent having a generally tubular structure, the surface of the structure being coated with a composition as described above, such that the biliary obstruction is eliminated.
  • tumor overgrowth of the common bile duct results in progressive cholestatic jaundice which is incompatible with life.
  • the biliary system which drains bile from the liver into the duodenum is most often obstructed by (1) a tumor composed of bile duct cells (cholangiocarcinoma), (2) a tumor which invades the bile duct (e.g., pancreatic carcinoma), or (3) a tumor which exerts extrinsic pressure and compresses the bile duct (e.g., enlarged lymph nodes).
  • a tumor composed of bile duct cells cholangiocarcinoma
  • a tumor which invades the bile duct e.g., pancreatic carcinoma
  • a tumor which exerts extrinsic pressure and compresses the bile duct e.g., enlarged lymph nodes.
  • Both primary biliary tumors, as well as other tumors which cause compression of the biliary tree may be treated utilizing the stents described herein.
  • One example of primary biliary tumors are adenocarcinomas (which are also called Klatskin tumors when found at the bifurcation of the common hepatic duct). These tumors are also referred to as biliary carcinomas, choledocholangiocarcinomas, or adenocarcinomas of the biliary system.
  • Benign tumors which affect the bile duct e.g., adenoma of the biliary system
  • squamous cell carcinomas of the bile duct and adenocarcinomas of the gallbladder may also cause compression of the biliary tree, and therefore, result in biliary obstruction.
  • Compression of the biliary tree is most commonly due to tumors of the liver and pancreas which compress and therefore obstruct the ducts. Most of the tumors from the pancreas arise from cells of the pancreatic ducts. This is a highly fatal form of cancer (5% of all cancer deaths; 26,000 new cases per year in the U.S.) with an average of 6 months survival and a 1 year survival rate of only 10%. When these tumors are located in the head of the pancreas they frequently cause biliary obstruction, and this detracts significantly from the quality of life of the patient.
  • pancreatic tumors While all types of pancreatic tumors are generally referred to as "carcinoma of the pancreas," there are histologic subtypes including: adenocarcinoma, adenosquamous carcinoma, cystadeno-carcinoma, and acinar cell carcinoma. Hepatic tumors, as discussed above, may also cause compression of the biliary tree, and therefore cause obstruction of the biliary ducts.
  • a biliary stent is first inserted into a biliary passageway in one of several ways: from the top end by inserting a needle through the abdominal wall and through the liver (a percutaneous transhepatic cholangiogram or "PTC”); from the bottom end by cannulating the bile duct through an endoscope inserted through the mouth, stomach, or duodenum (an endoscopic retrograde cholangiogram or "ERCP”); or by direct incision during a surgical procedure.
  • PTC percutaneous transhepatic cholangiogram
  • ERCP endoscopic retrograde cholangiogram
  • a preinsertion examination, PTC, ERCP, or direct visualization at the time of surgery should generally be performed to determine the appropriate position for stent insertion.
  • a guidewire is then advanced through the lesion, and over this a delivery catheter is passed to allow the stent to be inserted in its collapsed form.
  • the diagnostic exam was a PTC
  • the guidewire and delivery catheter will be inserted via the abdominal wall, while if the original exam was an ERCP the stent will be placed via the mouth.
  • the stent is then positioned under radiologic, endoscopic, or direct visual control taking particular care to place it precisely across the narrowing in the bile duct.
  • the delivery catheter will be removed leaving the stent standing as a scaffolding which holds the bile duct open. A further cholangiogram will be performed to document that the stent is appropriately positioned.
  • esophageal obstructions comprising inserting an esophageal stent into an esophagus, the stent having a generally tubular structure, the surface of the structure being coated with an anti-angiogenic composition as described above, such that the esophageal obstruction is eliminated.
  • the esophagus is the hollow tube which transports food and liquids from the mouth to the stomach. Cancer of the esophagus or invasion by cancer arising in adjacent organs (e.g., cancer of the stomach or lung) results in the inability to swallow food or saliva.
  • a preinsertion examination usually a barium swallow or endoscopy should generally be performed in order to determine the appropriate position for stent insertion.
  • a catheter or endoscope may then be positioned through the mouth, and a guidewire is advanced through the blockage.
  • a stent delivery catheter is passed over the guidewire under radiologic or endoscopic control, and a stent is placed precisely across the narrowing in the esophagus.
  • a post insertion examination usually a barium swallow x-ray, may be utilized to confirm appropriate positioning.
  • tracheal/bronchial obstructions comprising inserting a tracheal/bronchial stent into the trachea or bronchi, the stent having a generally tubular structure, the surface of which is coated with an anti-angiogenic composition as described above, such that the tracheal/bronchial obstruction is eliminated.
  • the trachea and bronchi are tubes which carry air from the mouth and nose to the lungs.
  • preinsertion examination should generally be performed in order to determine the appropriate position for stent insertion.
  • a catheter or endoscope is then positioned through the mouth, and a guidewire advanced through the blockage.
  • a delivery catheter is then passed over the guidewire in order to allow a collapsed stent to be inserted.
  • the stent is placed under radiologic or endoscopic control in order to place it precisely across the narrowing.
  • the delivery catheter may then be removed leaving the stent standing as a scaffold on its own.
  • a post insertion examination usually a bronchoscopy, may be utilized to confirm appropriate positioning.
  • urethral obstructions comprising inserting a urethral stent into a urethra, the stent having a generally tubular structure, the surface of the structure being coated with an anti-angiogenic composition as described above, such that the urethral obstruction is eliminated.
  • the urethra is the tube which drains the bladder through the penis. Extrinsic narrowing of the urethra as it passes through the prostate, due to hypertrophy of the prostate, occurs in virtually every man over the age of 60 and causes progressive difficulty with urination.
  • a preinsertion examination usually an endoscopy or urethrogram should generally first be performed in order to determine the appropriate position for stent insertion, which is above the external urinary sphincter at the lower end, and close to flush with the bladder neck at the upper end.
  • An endoscope or catheter is then positioned through the penile opening and a guidewire advanced into the bladder.
  • a delivery catheter is then passed over the guidewire in order to allow stent insertion.
  • the delivery catheter is then removed, and the stent expanded ini olace.
  • a post insertion examination usually endoscopy or retrograde urethrogram, may be utilized to confirm appropriate position.
  • vascular obstructions comprising inserting a vascular stent into a blood vessel, the stent having a generally tubular structure, the surface of the structure being coated with an anti-angiogenic composition as described above, such that the vascular obstruction is eliminated.
  • stents may be placed in a wide array of blood vessels, both arteries and veins, to prevent recurrent stenosis at the site of failed angioplasties, to treat narrowings that would likely fail if treated with angioplasty, and to treat post surgical narrowings (e.g., dialysis graft stenosis).
  • anti-angiogenic compositions may be utilized in a wide variety of surgical procedures.
  • an anti-angiogenic compositions in the form of, for example, a spray or film
  • an anti-angiogenic compositions may be utilized to coat or spray an area prior to removal of a tumor, in order to isolate normal surrounding tissues from malignant tissue, and/or to prevent the spread of disease to surrounding tissues.
  • anti-angiogenic compositions e.g., in the form of a spray
  • methods for treating tumor excision sites, comprising administering an anti- angiogenic composition as described above to the resection margins of a tumor subsequent to excision, such that the local recurrence of cancer and the formation of new blood vessels at the site is inhibited.
  • the anti-angiogenic composition(s) or anti-angiogenic factor(s) alone
  • are administered directly to the tumor excision site e.g., applied by swabbing, brushing or otherwise coating the resection margins of the tumor with the anti-angiogenic composition(s) or factor(s)
  • the anti- angiogenic composition(s) or factor(s) may be incorporated into known surgical pastes prior to administration.
  • the anti-angiogenic compositions are applied after hepatic resections for malignancy, and after neurosurgical operations.
  • anti-angiogenic compositions may be administered to the resection margin of a wide variety of tumors, including for example, breast, colon, brain and hepatic tumors.
  • anti- angiogenic compositions may be administered to the site of a neurological tumor subsequent to excision, such that the formation of new blood vessels at the site are inhibited.
  • the brain is highly functionally localized; le., each s p ecific anatomical region is specialized to carry out a specific function. Therefore it is the location of brain pathology that is often more important than the type. A relatively small lesion in a key area can be far more devastating than a much larger lesion in a less important area.
  • a lesion on the surface of the brain may be easy to resect surgically, while the same tumor located deep in the brain may not (one would have to cut through too many vital structures to reach it).
  • benign tumors can be dangerous for several reasons: they may grow in a key area and cause significant damage; even though they would be cured by surgical resection this may not be possible; and finally, if left unchecked they can cause increased intracranial pressure.
  • the skull is an enclosed space incapable of expansion. Therefore, if something is growing in one location, something else must be being compressed in another location - the result is increased pressure in the skull or increased intracranial pressure. If such a condition is left untreated, vital structures can be compressed, resulting in death.
  • CNS central nervous system
  • brain tumors which may be treated utilizing the compositions and methods described herein include Glial Tumors (such as Anaplastic Astrocytoma, Glioblastoma Multiform, Pilocytic Astrocytoma, Oligodendroglioma, Ependymoma, Myxopapillary Ependymoma, Subependymoma, Choroid Plexus Papilloma); Neuron Tumors (e.g., Neuroblastoma, Ganglioneuroblastoma, Ganglioneuroma, and
  • corneal neovascularization e.g., trachoma, herpes simplex keratitis, leishmaniasis and onchocerciasis
  • corneal infections e.g., trachoma, herpes simplex keratitis, leishmaniasis and onchocerciasis
  • immunological processes e.g., graft rejection and Stevens-Johnson's syndrome
  • alkali burns e.g., trauma, inflammation (of any cause), toxic and nutritional deficiency states, and as a complication of wearing contact lenses.
  • the cause of corneal neovascularization may vary, the response of the cornea to the insult and the subsequent vascular ingrowth is similar regardless of the cause. Briefly, the location of the injury appears to be of importance as only those lesions situated within a critical distance of the limbus will incite an angiogenic response. This is likely due to the fact that the angiogenic factors responsible for eliciting the vascular invasion are created at the site of the lesion, and must diffuse to the site of the nearest blood vessels
  • an anti-angiogenic factor may be prepared for topical administration in saline (combined with any of the preservatives and antimicrobial agents commonly used in ocular preparations), and administered in eyedrop form.
  • the anti- angiogenic factor solution may be prepared in its pure form and administered several times daily.
  • anti-angiogenic compositions, prepared as described above may also be administered directly to the cornea.
  • the anti-angiogenic composition is prepared with a muco-adhesive polymer which binds to cornea.
  • the anti-angiogenic factors or anti-angiogenic compositions may be utilized as an adjunct to conventional steroid therapy.
  • the material could be injected in the perilimbic cornea interspersed between the corneal lesion and its undesired potential limbic blood supply.
  • Such methods may also be utilized in a similar fashion to prevent capillary invasion of transplanted corneas.
  • injections might only be required 2-3 times per year.
  • a steroid could also be added to the injection solution to reduce inflammation resulting from the injection itself.
  • methods for treating hypertrophic scars and keloids comprising the step of administering one of the above-described anti-angiogenic compositions to a hypertrophic scar or keloid.
  • inflammation occurs in response to an injury which is severe enough to break the skin.
  • blood and tissue fluid form an adhesive coagulum and fibrinous network which serves to bind the wound surfaces together.
  • proliferative phase in which there is ingrowth of capillaries and connective tissue from the wound edges, and closure of the skin defect.
  • the maturation process begins wherein the scar contracts and becomes less cellular, less vascular, and appears flat and white. This final phase may take between 6 and 12 months.
  • the scar may become red and raised. If the scar remains within the boundaries of the original wound it is referred to as a hypertrophic scar, but if it extends beyond the original scar and into the surrounding tissue, the lesion is referred to as a keloid. Hypertrophic scars and keloids are produced during the second and third phases of scar formation. Several wounds are particularly prone to excessive endothelial and fibroblastic proliferation, including burns, open wounds, and infected wounds. With hypertrophic scars, some degree of maturation occurs and gradual improvement occurs. In the case of keloids however, an actual tumor is produced which can become quite large. Spontaneous improvement in such cases rarely occurs.
  • anti-angiogenic factors alone, or anti-angiogenic compositions as described above are directly injected into a hypertrophic scar or keloid in order to prevent the progression of these lesions.
  • the frequency of injections will depend upon the release kinetics of the polymer used (if present), and the clinical response.
  • This therapy is of particular value in the prophylactic treatment of conditions which are known to result in the development of hypertrophic scars and keloids (e.g., burns), and is preferably initiated after the proliferative phase has had time to progress (approximately 14 days after the initial injury), but before hypertrophic scar or keloid development.
  • Neovascular glaucoma generally occurs as a complication of diseases in which retinal ischemia is predominant. In particular, about one third of the patients with this disorder have diabetic retinopathy and 28% have central retinal vein occlusion. Other causes include chronic retinal detachment, end-stage glaucoma, carotid artery obstructive disease, retrolental fibroplasia, sickle-cell anemia, intraocular tumors, and carotid cavernous fistulas. In its early stages, neovascular glaucoma may be diagnosed by high magnification slitlamp biomicroscopy, where it reveals small, dilated, disorganized capillaries (which leak fluorescein) on the surface of the iris. Later gonioscopy demonstrates progressive obliteration of the anterior chamber angle by fibrovascular bands. While the anterior chamber angle is still open, conservative therapies may be of assistance. However, once the angle closes surgical intervention is required in order to alleviate the pressure.
  • anti- angiogenic factors may be administered topically to the eye in order to treat early forms of neovascular glaucoma.
  • anti-angiogenic compositions may be implanted by injection of the composition into the region of the anterior chamber angle. This provides a sustained localized increase of anti-angiogenic factor, and prevents blood vessel growth into the area. Implanted or injected anti-angiogenic compositions which are placed between the advancing capillaries of the iris and the anterior chamber angle can "defend" the open angle from neovascularization. As capillaries will not grow within a significant radius of the anti-angiogenic composition, patency of the angle could be maintained.
  • the anti-angiogenic composition may also be placed in any location such that the anti-angiogenic factor is continuously released into the aqueous humor.
  • proliferative diabetic retinopathy may be treated by injection of an anti-angiogenic factor(s) (or anti-angiogenic composition) into the aqueous humor or the vitreous, in order to increase the local concentration of anti- angiogenic factor in the retina.
  • this treatment should be initiated prior to the acquisition of severe disease requiring photocoagulation.
  • arteries which feed the neovascular lesions may be embolized (utilizing anti-angiogenic compositions, as described above)
  • methods for treating retrolental fibroblasia, comprising the step of administering a therapeuticaUy effective amount of an anti-angiogenic factor (or anti-angiogenic composition) to the eye, such that the formation of blood vessels is inhibited.
  • retrolental fibroblasia is a condition occurring in premature infants who receive oxygen therapy.
  • the peripheral retinal vasculature particularly on the temporal side, does not become fully formed until the end of fetal life.
  • Excessive oxygen (even levels which would be physiologic at term) and the formation of oxygen free radicals are thought to be important by causing damage to the blood vessels of the immature retina. These vessels constrict, and then become structurally obliterated on exposure to oxygen.
  • the peripheral retina fails to vascularize and retinal ischemia ensues.
  • neovascularization is induced at the junction of the normal and the ischemic retina.
  • vascular grafts are synthetic tubes, usually made of Dacron or Gortex, inserted surgically to bypass arterial blockages, most frequently from the aorta to the femoral, or the femoral to the popliteal artery.
  • a major problem which particularly complicates femoral-popliteal bypass grafts is the formation of a subendothelial scar-like reaction in the blood vessel wall called neointimal hyperplasia, which narrows the lumen within and adjacent to either end of the graft, and which can be progressive.
  • the cartilage extract is passed through gauze netting in order to remove the larger constituents.
  • the filtrate is then passed through an Amicon ultrafiltration unit which utilizes spiral-wound cartridges, with a molecular weight cutoff of 100,000.
  • the filtrate (containing proteins with a molecular weight of less than 100,000 daltons) is then dialyzed against 0.02 M MES buffer (pH 6) with an Amicon ultrafiltration unit which retains proteins with a molecular weight of greater than 3,000 daltons. Utilizing this method, low molecular weight proteins and constituents are removed, as well as excessive amounts of guanidium HCl.
  • the dialysate is concentrated to a final concentration 9 mg/ml.
  • Figures 1-4 Results of the above experiments are shown in Figures 1-4. Briefly, the general features of the normal chick shell-less egg culture are shown in Figure 1A. At day 6 of incubation, the embryo is centrally positioned to a radially expanding network of blood vessels; the CAM develops adjacent to the embryo. These growing vessels lie close to the surface and are readily visible making this system an idealized model for the study of angiogenesis. Living, unstained capillary networks of the CAM can be imaged no ⁇ invasively with a stereomicroscope. Figure IB illustrates such a vascular area in which the cellular blood elements within capillaries were recorded with the use of a video/computer interface.
  • each CAM was examined under living conditions with a stereomicroscope equipped with a video/computer interface in order to evaluate the effects on angiogenesis.
  • This imaging setup was used at a magnification of 160 times which permitted the direct visualization of blood cells within the capillaries thereby blood flow in areas of interest could be easily assessed and recorded.
  • the inhibition of angiogenesis was defined as an area of the CAM devoid of a capillary network ranging from 2 - 6 mm in diameter. Areas of inhibition lacked vascular blood flow and thus were only observed under experimental conditions of methylcellulose containing taxol; under control conditions of disks lacking taxol there was no effect on the developing capillary system.
  • Table II The dose-dependent, experimental data of the effects of taxol at different concentrations are shown in Table II. TABLE II
  • CAM are readily apparent at both the light and electron microscopic levels. For the convenience of presentation, three distinct phases of general transition from the normal to the avascular state are shown. Near the periphery of the avascular zone the CAM is hallmarked by an abundance of mitotic cells within all three germ layers ( Figures 3A and 4A). This enhanced mitotic division was also a consistent observation for capillary endothelial cells. However, the endothelial cells remained junctionally intact with no extravasation of blood cells. With further degradation, the CAM is characterized by the breakdown and dissolution of capillaries ( Figures 3B and 4B).
  • the presumptive endothelial cells typically arrested in mitosis, still maintain a close spatial relationship with blood cells and lie subjacent to the ectoderm; however, these cells are not junctionally linked.
  • the most central portion of the avascular zone was characterized by a thickened ectodermal and endodermal layer (Figures 3C and 4C). Although these layers were thickened, the cellular junctions remained intact and the layers maintained their structural characteristics. Within the mesoderm, scattered mitotically arrested cells were abundant; these cells did not exhibit the endothelial cell polarization observed in the former phase. Also, throughout this avascular region, degenerating cells were common as noted by the electron dense vacuoles and cellular debris (Figure 4C).
  • Taxol-treated avascular zones also revealed an abundance of cells arrested in mi.osis in all three germ layers of the CAM; this was unique to taxol since no previous study has illustrated such an event.
  • endothelial cells could not undergo their normal metabolic functions involved in angiogenesis.
  • the avascular zone formed by suramin and cortisone acetate do not produce mitotically arrested cells in the CAM; they only prevented further blood vessel growth into the treated area. Therefore, even though agents are anti-angiogenic, there are many points in which the angiogenesis process may be targetted.
  • 5% ELVAX poly(ethylene-vinyl acetate) cross ⁇ linked with 5% vinyl acetate
  • DCM dichloromethane
  • PVA Polyvinyl Alcohol
  • Tubes containing different weights of the drug are then suspended in a multi- sample water bath at 40° for 90 minutes with automated stirring. The mixes are removed, and microsphere samples taken for size analysis. Tubes are centrifuged at lOOOg for 5 min. The PVA supernatant is removed and saved for analysis (nonencapsulated drug).
  • microspheres are then washed (vortexed) in 5 ml of water and recentrifuged. The 5 ml wash is saved for analysis (surface bound drug).
  • Microspheres are then wetted in 50 ul of methanol, and vortexed in 1 ml of DCM to dissolve the ELVAX. The microspheres are then warmed to 40°C, and 5 ml of 50°C water is slowly added with stirring. This procedure results in the immediate evaporation of DCM, thereby causing the release of sodium suramin into the 5 ml of water. All three 5 ml samples were then assayed for drug content.
  • Sodium suramin absorbs uv/vis with a lambda max of 312nm.
  • Results are shown in Figures 5-10. Briefly, the size distribution of microspheres appears to be unaffected by inclusion of the drug in the DCM (see Figures 5 and 6). Good yields of microspheres in the 20 to 60 ⁇ m range may be obtained.
  • Fisher rats weighing approximately 300 grams are anesthetized, and a 1 cm transverse upper abdominal incision is made.
  • Two-tenths of a milliliter of saline containing 1 x 10" live 9L gliosarcoma cells are injected into 2 of the 5 hepatic lobes by piercing a 27 gauge needle 1 cm through the liver capsule.
  • the abdominal wound is closed with 6.0 resorptible suture and skin clips and the GA terminated.
  • the abdominal wound is closed with 6.0 resorptible suture with skin clips, and the anesthetic terminated.
  • the rat is returned to the animal care facility to have a standard diet for 14 days, at which time each tumor deposit will measure 1 cm in diameter.
  • the same procedure is repeated using Westar rats and a Colon Cancer cell line (Radiologic Oncology Lab, M.D. Anderson, Houston, Texas). In this instance, 3 weeks are required post- injection for the tumor deposits to measure 1 cm in diameter each.
  • the same general anesthetic procedure is followed and a midline abdominal incision is performed.
  • the duodenum is flipped and the gastroduodenal artery is identified and mobilized.
  • Ties are placed above and below a cutdown site on the midportion of the gastroduodenal artery (GDA), and 0.038 inch polyethylene tubing is introduced in a retrograde fashion into the artery using an operating microscope. The tie below the insertion point will ligate the artery, while the one above will fix the catheter in place.
  • Angiography is performed by injecting 0.5 ml of 60% radiopaque contrast material through the catheter as an x-ray is taken.
  • the rats are subsequently sacrificed at 2, 7, 14, 21 and 84 days post-embolization in order to determine efficacy of the anti-angiogenic factor.
  • general anesthetic is given, and utilizing aseptic precautions, a midline incision performed.
  • the GDA is mobilized again, and after placing a ligature near the junction of the GDA and the hepatic artery (i.e., well above the site of the previous cutdow ⁇ ), a 0.038-inch polyethylene tubing is inserted via cutdown of the vessel and angiography is performed.
  • the rat is then euthanized by injecting Euthanyl into the dorsal vein of the tail. Once euthanasia is confirmed, the liver is removed en bloc along with the stomach, spleen and both lungs.
  • Histologic analysis is performed on a prepared slide stained with hematoxylin and eosin ("H and E") stain. Briefly, the lungs are sectioned at 1 cm intervals to assess passage of embolic material through the hepatic veins and into the right side of circulation. The stomach and spleen are also sectioned in order to assess inadvertent immobilization from reflux of particles into the celiac access of the collateral circulation.
  • H and E hematoxylin and eosin
  • a plain abdominal X-ray is performed at 2 days in order to assess the degree of stent opening. Rats are sacrificed at 2, 7, 14, 28 and 56 days post- stent insertion by injecting Euthanyl, and their livers removed en bloc once euthanasia is confirmed. After fixation in formaldehyde for 48 hours, the liver is sectioned at 0.5 mm intervals; including severing the stent transversely using a fresh blade for each slice. Histologic sections stained with H and E are then analyzed to assess the degree of tumor ingrowth into the stent lumen.
  • microspheres After the microspheres have sat at room temperature overnight, a 5 ml automatic pipetter or vacuum suction is used to draw the supernatant off of the sedimented microspheres.
  • the microspheres are allowed to dry in the uncapped vial in a drawer for a period of one week or until they are fully dry (vial at constant weight). Faster drying may be accomplished by leaving the uncapped vial under a slow stream of nitrogen gas (flow approx. 10 ml/min.) in the fume hood. When fully dry (vial at constant weight), the vial is weighed and capped. The labelled, capped vial is stored at room temperature in a drawer. Microspheres are normally stored no longer than 3 months.
  • compositions may be produced: (1) as a "thermopaste” that is applied to a desired site as a fluid, and hardens to a solid of the desired shape at a specified temperature (e.g., body temperature); (2) as a spray (Le., "nanospray") which may delivered to a desired site either directly or through a specialized apparatus (e.g., endoscopy), and which subsequently hardens to a solid which adheres to the tissue to which it is applied; (3) as an adherent, pliable, resilient, angiogeneis inhibitor-polymer film applied to a desired site either directly or through a specialized apparatus, and which preferably adheres to the site to which it is applied; and (4) as a fluid composed of a suspension of microspheres in an appropriate carrier medium, which is applied to a desired site either directly or via a specialized apparatus, and which leaves
  • Reagents and equipment which are utilized within the following experiments include a sterile glass syringe (1 ml), Corning hot plate/stirrer, 20 ml glass scintillation vial, moulds (e.g., 50 ⁇ l DSC pan or 50 ml centrifuge tube cap inner portion), scalpel and tweezers, Polycaprolactone ("PCL" - mol wt 10,000 to 20,000; Polysciences, Warrington, Pennsylvania USA), and Taxol (Sigma grade 95% purity minimum).
  • PCL Polycaprolactone
  • the syringe may be reheated to 60°C and administered as a liquid which solidifies when cooled to body temperature.
  • Nanospray is a suspension of small microspheres in saline. If the microspheres are very small (i.e., under 1 ⁇ m in diameter) they form a colloid so that the suspension will not sediment under gravity. As is described in more detail below, a suspension of 0.1 ⁇ m to 1 ⁇ m microparticles may be created suitable for deposition onto tissue through a finger pumped aerosol.
  • Equipment and materials which may be utilized to produce nanospray include 200 ml water jacketed beaker (Kimax or Pyrex), Haake circulating water bath, overhead stirrer and controller with 2 inch diameter (4 blade, propeller type stainless steel stirrer; Fisher brand), 500 ml glass beaker, hot plate/stirrer (Corning brand), 4 X 50 ml polypropylene centrifuge tubes (Nalgene), glass scintillation vials with plastic insert caps, table top centrifuge (Beckman), high speed centrifuge - floor model (JS 21 Beckman), Mettler analytical balance (AJ 100, 0.1 mg), Mettler digital top loading balance (AE 163, 0.01 mg), automatic pipetter (Gilson), sterile pipette tips, pump action aerosol (Pfeiffer pharmaceuticals) 20 ml, laminar flow hood, Polycaprolactone ("PCL” - mol wt 10,000 to 20,000; Polysciences, Warrington, Pennsylvania USA), "washed”
  • the solution can be prepared by following the procedure given below, or by diluting the 5% (w/v) PVA stock solution prepared for production of microspheres (see Example 8). Briefly, 17.5 g of PVA is weighed directly into a 600 ml glass beaker, and 500 ml of distilled water is added. Place a 3 inch teflon coated stir bar in the beaker. Cover the beaker with a cover glass to reduce evaporation losses. Place the beaker in a 2000 ml glass beaker containing 300 ml of water. This will act as a water bath. Stir the PVA at 300 rpm at 85°C (Corning hot plate/stirrer) for 2 hours or until fully dissolved.
  • Dissolving of the PVA can be determined by a visual check; the solution should be clear. Use a pipette to transfer the solution to a glass screw top storage container and store at 4°C for a maximum of two months. This solution should be warmed to room temperature before use or dilution.
  • polymer/drug e.g., taxol
  • Procedure for Producing Films - Sprayed Weigh sufficient polymer directly into a 20 ml glass scintillation vial and add sufficient DCM to achieve a 2% w/v solution. Cap the vial and mix the solution to dissolve the polymer (hand shaking). Assemble the moulds in a vertical orientation in a suitable mould holding apparatus in the fume hood. Position this mould holding apparatus 6 to 12 inches above the fume hood floor on a suitable support (e.g., inverted 2000 ml glass beaker) to enable horizontal spraying. Using an automatic pipette, transfer a suitable volume (minimum 5 ml) of the 2% polymer solution to a separate 20 ml glass scintillation vial.
  • a suitable volume minimum 5 ml
  • Reagents and equipment which were utilized within these experiments include glass beakers, Carbopol 925 (pharmaceutical grade, Goodyear Chemical Co.), distilled water, sodium hydroxide (1 M) in water solution, sodium hydroxide solution (5 M) in water solution, microspheres in the
  • Taxol loaded microspheres (0.6% w/w taxol) are prepared by dissolving the taxol in the 5% w/v polymer solution in DCM.
  • the polymer blend used is 50:50 EVA:PLA.
  • a "large" size fraction and "small” size fraction of microspheres are produced by adding the taxol/polymer solution dropwise into 2.5% w/v PVA and 5% w/v PVA, respectively.
  • the dispersions are stirred at 40°C at 200 rpm for 2 hours, centrifuged and washed 3 times in water as described previously.
  • Microspheres are air dried and samples are sized using an optical microscope with a stage micrometer. Over 300 microspheres are counted per sample. Control microspheres (taxol absent) are prepared and sized as described previously.
  • Microspheres are placed on sample holders, sputter coated with gold and micrographs obtained using a Philips 501B SEM operating at 15 kV.
  • Figure 16B shows CAMs treated with control PCL microspheres
  • Figure 16C shows treatment with 5% taxol loaded microspheres.
  • the CAM with the control microspheres shows a normal capillary network architecture.
  • the CAM treated with taxol-PCL microspheres shows marked vascular regression and zones which are devoid of a capillary network.
  • the initial rapid or burst phase of taxol release is thought to be due to diffusional release of the drug from the superficial region of the microspheres (close to the microsphere surface). Release of taxol in the second (slower) phase of the release profiles is not likely due to degradation or erosion of PCL because studies have shown that under in vitro conditions in water there is no significant weight loss or surface erosion of PCL over a 7.5-week period.
  • the slower phase of taxol release is probably due to dissolution of the drug within fluid-filled pores in the polymer matrix and diffusion through the pores.
  • the greater release rate at higher taxol loading is probably a result of a more extensive pore network within the polymer matrix. Taxol microspheres with 5% loading have been shown to release sufficient drug to produce extensive inhibition of angiogenesis when placed on the CAM. The inhibition of blood vessel growth resulted in an avascular zone as shown in Figure 16C.
  • the melting point of PCL/MePEG polymer blends may be determined by differential scanning calorimetry from 30°C to 70°C at a heating rate of 2.5°C per minute. Results of this experiment are shown in Figures 18A and 18B. Briefly, as shown in Figure 18 A the melting point of the polymer blend (as determined by thermal analysis) is decreased by MePEG in a concentration dependent manner. The melting point of the polymer blends as a function of MePEG concentration is shown in Figure 18A. This lower melting point also translates into an increased time for the polymer blends to solidify from melt as shown in Figure 18B. A 30:70 blend of MePEG:PCL takes more than twice as long to solidify from the fluid melt than does PCL alone.
  • Thermopastes are made up containing 20% MePEG in PCL and loaded with between 0.2% and 10% taxol.
  • the release of taxol over time is measured as described above.
  • Figure 18F the amount of taxol released over time increases with increased taxol loading.
  • Figure 18G the order is reversed ( Figure 18G). This gives information about the residual taxol remaining in the paste and, if assumptions are made about the validity of extrapolating this data, allows for a projection of the period of time over which taxol will be released from the 20% MePEG Thermopaste.
  • Taxol is incorporated into thermopaste at concentrations of 5%, 10%, and 20% (w/v) essentially as described above (see Example 10), and used in the following experiments. Dried cut thermopaste is then heated to 60°C and pressed between two sheets of parafilm, flattening it, and allowing it to cool. Six embryos received 20% taxol-loaded thermopaste and 6 embryos received unloaded thermopaste prepared in this manner. One embryo died in each group leaving 5 embryos in each of the control and treated groups.
  • thermopaste and thermopaste containing 20% taxol was also heated to 60°C and placed directly on the growing edge of each CAM at day 6 of incubation; two embryos each were treated in this manner.
  • thermopaste with 10% taxol was applied to 11 CAMs and unloaded thermopaste was applied to an additional 11 CAMs, while 5% taxol- loaded thermopaste was applied to 10 CAMs and unloaded thermopaste was applied to 10 other control CAMs.
  • a 2 day exposure day 8 of incubation
  • the vasculature was examined with the aid of a stereomicroscope.
  • Liposyn II a white opaque solution, was injected into the CAM to increase the visibility of the vascular details.
  • the 20% taxol-loaded thermopaste showed extensive areas of avascularity (see Figure 19B) in all 5 of the CAMs receiving this treatment.
  • the highest degree of inhibition was defined as a region of avascularity covering 6 mm by 6 mm in size. All of the CAMs treated with 20% taxol-loaded thermopaste displayed this degree of angiogenesis inhibition.
  • Fertilized domestic chick embryos are incubated for 3 days prior to having their shells removed.
  • the egg contents are emptied by removing the shell located around the airspace, severing the interior shell membrane, perforating the opposite end of the shell and allowing the egg contents to gently slide out from the blunted end.
  • the contents are emptied into round-bottom sterilized glass bowls, covered with petri dish covers and incubated at 90% relative humidity and 3% carbon dioxide (see Example 2).
  • the murine MDAY-D2 tumor model may be used to examine the effect of local slow release of the chemotherapeutic and anti-angiogenic compounds such as taxol on tumor growth, tumor metastasis, and animal survival.
  • the MDAY-D2 tumor cell line is grown in a cell suspension consisting of 5% Fetal Calf Serum in alpha mem media. The cells are incubated at 37°C in a humidified atmosphere supplemented with 5% carbon dioxide, and are diluted by a factor of 15 every 3 days until a sufficient number of cells are obtained. Following the incubation period the cells are examined by light microscopy for viability and then are centrifuged at 1500 rpm for 5 minutes. PBS is added to the cells to achieve a dilution of 1,000,000 cells per ml.
  • mice Ten week old DBA/2J female mice are acclimatized for 3-4 days after arrival. Each mouse is then injected subcutaneously in the posteriolateral flank with 100,000 MDAY-D2 cells in 100 ml of PBS. Previous studies have shown that this procedure produces a visible tumor at the injection site in 3-4 days, reach a size of 1.0-1.7g by 14 days, and produces visible metastases in the liver 19-25 days post-injection. Depending upon the objective of the study a therapeutic intervention can be instituted at any point in the progression of the disease.
  • mice are injected with 140,000 MDAY-D2 cells s.c. and the tumors allowed to grow.
  • the mice are divided into groups of 5.
  • the tumor site was surgically opened under anesthesia, the local region treated with the drug-loaded thermopaste or control thermopaste without disturbing the existing tumor tissue, and the wound was closed.
  • the groups of 5 received either no treatment (wound merely closed), polymer (PCL) alone, 10% taxol-loaded thermopaste, or 20% taxol-loaded thermopaste (only 4 animals injected) implanted adjacent to the tumor site.
  • the weights of the tumors for each animal is shown in the table below:
  • AS a sterile, pliable, stretchable drug-polymer compound would be useful during cancer resection procedures. Often it is desirable to isolate the normal surrounding tissues from malignant tissue during resection operations to prevent iatrogenic spread of the disease to adjacent organs through inadvertent contamination by cancer cells. A drug-loaded parafilm could be stretched across normal tissues prior to manipulation of the tumor. This would be most useful if placed around the liver and other abdominal contents during bowel cancer resection surgery to prevent intraperitoneal spread of the disease to the liver. A biodegradable film could be left in situ to provide continued protection.
  • Incision sites are also a common location of post-operative recurrence of malignancy. This is thought to be due to contamination of the wound site with tumor cells during the surgical procedure. To address these issues, experiments are being conducted to determine the ability of angiogenesis inhibitor-loaded films to prevent this phenomenon.
  • Surgical films are prepared as described in Example 10. Thin films measuring approximately 1 cm x 1 cm are prepared containing either polymer alone (PCL) or PCL loaded with 5% taxol.
  • Rat Hepatic Tumor Model In an initial study Wistar rats weighing approximately 300 g underwent general anesthesia and a 3-5 cm abdominal incision is made along the midline. In the largest hepatic lobe, a 1 cm incision is made in the hepatic parenchyma and part of the liver edge is resected. A concentration of 1 million live 9L Glioma tumor cells (eluted from tissue culture immediately prior to the procedure) suspended in 100 ml of phosphate buffered saline are deposited onto the cut liver edge with a 30 gauge needle. The surgical is then placed over the cut liver edge containing the tumor cells and affixed in place with Gelfoam.
  • livers treated with polymer alone Both livers treated with polymer plus taxol are completely free of tumour when examined histologically. Also of importance, the liver capsule had regenerated and grown completely over the polymeric film and the cut surface of the liver indicating that there is no significant effect on wound healing. There is no evidence of local hepatic toxicity surrounding any (drug-loaded or drug-free) of the surgical films.
  • Taxol has been chosen for the initial studies because it is a potent inhibitor of neovascularization. In this manner, taxol in high local concentrations will prove to be a disease modifying agent in arthritis.
  • Three rabbits are injected intra-articularly with 0.5-5.0 ⁇ m, 10-30 ⁇ m, or 30-80 ⁇ m microspheres in a total volume of 0.2 mis (containing 0.5 mg of microspheres).
  • the joints are assessed visually (clinically) on a daily basis. After two weeks the animals are sacrificed and the joints examined histologically for evidence of inflammation and depletion of proteoglycans.
  • the rabbit inflammatory arthritis and osteoarthritis models are being used to evaluate the use of microspheres in reducing synovitis and cartilage degradation.
  • Degenerative arthritis is induced by a partial tear of the cruciate ligament and meniscus of the knee. After 4 to 6 weeks, the rabbits develop erosions in the cartilage similar to that observed in human osteoarthritis.
  • Inflammatory arthritis is induced by immunizing rabbits with bovine serum albumen (BSA) in Complete Freund's Adjuvent (CFA). After v 3 weeks, rabbits containing a high titer of anti-BSA antibody receive an intra- articular injection of BSA (5 mg). Joint swelling and pronounced synovitis is apparent by seven days, a proteoglycan depletion is observed by 7 to 14 days, and cartilage erosions are observed by 4 to 6 weeks.
  • BSA bovine serum albumen
  • CFA Complete Freund's Adjuvent
  • Inflammatory arthritis is induced as described above. After 4 days, the joints are injected with microspheres containing 5% taxol or vehicle. One group of animals will be sacrificed on day 14 and another on day 28. The joints are examined histologically for inflammation and cartilage degradation. The experiment is designed to determine if taxol microspheres can affect joint inflammation and cartilage matrix degradation.
  • Angiogenesis-inhibitor microspheres may be further examined in an osteoarthritis model. Briefly, degenerative arthritis is induced in rabbits as described above, and the joints receive an intra-articular injection of microspheres (5% taxol or vehicle only) on day 4. The animals are sacrificed on day 21 and day 42 and the joints examined histologically for evidence of cartilage degradation. Studies are conducted to assess angiogenesis inhibitors delivered via intra-articular microspheres as chondroprotective agents. Results
  • Figure 22A is a photograph of synovium from PBS injected joints.
  • Figure 22B is a photograph of joints injected with microspheres.
  • Figure 22C is a photograph of cartilage from joints injected with PBS, and
  • Figure 22D is a photograph of cartilage from joints injected with microspheres.
  • Microspheres can be injected intra-articularly without causing any discernible changes to the joint surface. This indicates that this method may be an effective means of delivering a targeted, sustained-release of disease- modifying agents to diseased joints, while minimizing the toxicity which could be associated with the systemic administration of such biologically active compounds. As discussed above, microspheres can be formulated into specific sizes with defined drug release kinetics. It has also been demonstrated that taxol is a potent inhibitor of angiogenesis and that it is released from microspheres in quantities sufficient to block neovascularization on the CAM assay.
  • angiogenesis-inhibitor-loaded microspheres should be capable of blocking the neovasculariza t ion that occurs in diseases such as rheumatoid arthritis and leads to cartilage destruction in the joint.
  • the drug-loaded microspheres can act as a "chondroprotective" agent which protects the cartilage from irreversible destruction from invading neovascular pannus tissue.
PCT/CA1994/000373 1993-07-19 1994-07-19 Anti-angiogenic compositions and methods of use WO1995003036A1 (en)

Priority Applications (44)

Application Number Priority Date Filing Date Title
CA002167268A CA2167268C (en) 1993-07-19 1994-07-19 Anti-angiogenic compositions and methods of use
EP94920360A EP0706376B2 (en) 1993-07-19 1994-07-19 Anti-angiogenic compositions and methods of use
DE69403966T DE69403966T3 (de) 1993-07-19 1994-07-19 Anti-angiogene mittel und verfahren zu deren verwendung
JP50482395A JP3423317B2 (ja) 1993-07-19 1994-07-19 抗−血管形成性組成物およびそれにより被覆されたステント
DK94920360T DK0706376T4 (da) 1993-07-19 1994-07-19 Antiangiogene præparater og fremgangsmåder til anvendelse
AU71192/94A AU693797B2 (en) 1993-07-19 1994-07-19 Anti-angiogenic compositions and methods of use
KR1020117007294A KR101222904B1 (ko) 1993-07-19 1994-07-19 항맥관형성 조성물, 당해 조성물로 피복된 스텐트 및 당해 스텐트의 제조방법
NZ268326A NZ268326A (en) 1993-07-19 1994-07-19 Stent with a coating comprising an anti-angiogenic compound, such as taxol, and a polymeric carrier
DK01117873T DK1159974T3 (da) 1993-07-19 1994-07-19 Antiangiogene sammensætninger indeholdende taxol og en ikke-bionedbrydelig bærer og deres anvendelse
US08/472,413 US5886026A (en) 1993-07-19 1995-06-07 Anti-angiogenic compositions and methods of use
US08/478,914 US5994341A (en) 1993-07-19 1995-06-07 Anti-angiogenic Compositions and methods for the treatment of arthritis
US08/486,867 US20030203976A1 (en) 1993-07-19 1995-06-07 Anti-angiogenic compositions and methods of use
US08/478,203 US5716981A (en) 1993-07-19 1995-06-07 Anti-angiogenic compositions and methods of use
NO19960226A NO324275B1 (no) 1993-07-19 1996-01-18 Stenter og fremgangsmate for a fremstille slike
GR970402471T GR3024833T3 (en) 1993-07-19 1997-09-24 Anti-angiogenic compositions and methods of use
US08/984,258 US20020165265A1 (en) 1993-07-19 1997-12-03 Anti-angiogenic compositions and methods of use
US09/294,458 US6506411B2 (en) 1993-07-19 1999-04-19 Anti-angiogenic compositions and methods of use
US09/925,220 US6544544B2 (en) 1993-07-19 2001-08-08 Anti-angiogenic compositions and methods of use
US09/927,882 US20020119202A1 (en) 1993-07-19 2001-08-09 Anti-angiogenic compositions and methods of use
US10/112,921 US6846841B2 (en) 1993-07-19 2002-03-28 Anti-angiogenic compositions and methods of use
US10/389,262 US20040076672A1 (en) 1993-07-19 2003-03-13 Anti-angiogenic compositions and methods of use
US10/390,534 US20040062810A1 (en) 1993-07-19 2003-03-14 Anti-angiogenic compositions and methods of use
US10/959,349 US7820193B2 (en) 1993-07-19 2004-10-07 Anti-angiogenic compositions and methods of use
US10/959,398 US20050208137A1 (en) 1993-07-19 2004-10-07 Anti-angiogenic compositions and methods of use
US10/962,578 US20050042295A1 (en) 1993-07-19 2004-10-13 Anti-angiogenic compositions and methods of use
US11/151,399 US20060127445A1 (en) 1993-07-19 2005-06-14 Anti-angiogenic compositions and methods of use
US11/207,021 US20060035831A1 (en) 1993-07-19 2005-08-19 Anti-angiogenic compositions and methods of use
US11/206,993 US20060035830A1 (en) 1993-07-19 2005-08-19 Anti-angiogenic compositions and methods of use
US11/206,779 US20060034932A1 (en) 1993-07-19 2005-08-19 Anti-angiogenic compositions and methods of use
US11/207,058 US20060035832A1 (en) 1993-07-19 2005-08-19 Anti-angiogenic compositions and methods of use
US11/207,059 US20060035833A1 (en) 1993-07-19 2005-08-19 Anti-angiogenic compositions and methods of use
US11/332,170 US20060121117A1 (en) 1993-07-19 2006-01-17 Anti-angiogenic compositions and methods of use
US11/435,742 US20060240113A1 (en) 1993-07-19 2006-05-18 Anti-angiogenic compositions and methods of use
US11/435,780 US20070003629A1 (en) 1993-07-19 2006-05-18 Anti-angiogenic compositions and methods of use
US11/435,854 US20070003630A1 (en) 1993-07-19 2006-05-18 Anti-angiogenic compositions and methods of use
NO20073066A NO20073066L (no) 1993-07-19 2007-06-15 Anti-angiogen sammensetning, anordning inneholdende denne, fremgangsmate for fremstilling og anvendelse
US11/830,080 US20070298123A1 (en) 1993-07-19 2007-07-30 Anti-angiogenic compositions and methods of use
US11/830,186 US20080020063A1 (en) 1993-07-19 2007-07-30 Anti-angiogenic compositions and methods of use
US11/830,208 US20090074830A1 (en) 1993-07-19 2007-07-30 Anti-angiogenic compositions and methods of use
US11/830,240 US20080166387A1 (en) 1993-07-19 2007-07-30 Anti-angiogenic compositions and methods of use
US12/098,173 US20090036517A1 (en) 1993-07-19 2008-04-04 Anti-angiogenic compositions and methods of use
US12/817,682 US20110071612A1 (en) 1993-07-19 2010-06-17 Anti-angiogenic compositions and methods of use
US12/820,523 US20110066251A1 (en) 1993-07-19 2010-06-22 Anti-angiogenic compositions and methods of use
US12/820,614 US20110118825A1 (en) 1993-07-19 2010-06-22 Anti-angiogenic compositions and methods of use

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US9453693A 1993-07-19 1993-07-19
US08/094,536 1993-07-19

Related Parent Applications (1)

Application Number Title Priority Date Filing Date
US9453693A Continuation-In-Part 1993-07-19 1993-07-19

Related Child Applications (4)

Application Number Title Priority Date Filing Date
US9453693A Continuation-In-Part 1993-07-19 1993-07-19
US08417160 A-371-Of-International 1994-07-19
US48026095A Division 1993-07-19 1995-06-07
US08/478,914 Division US5994341A (en) 1993-07-19 1995-06-07 Anti-angiogenic Compositions and methods for the treatment of arthritis

Publications (1)

Publication Number Publication Date
WO1995003036A1 true WO1995003036A1 (en) 1995-02-02

Family

ID=22245764

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CA1994/000373 WO1995003036A1 (en) 1993-07-19 1994-07-19 Anti-angiogenic compositions and methods of use

Country Status (19)

Country Link
US (23) US6506411B2 (un)
EP (13) EP1159975B1 (un)
JP (4) JP3423317B2 (un)
KR (5) KR100389223B1 (un)
CN (7) CN100998565A (un)
AT (10) ATE537858T1 (un)
AU (1) AU693797B2 (un)
CA (4) CA2472373C (un)
DE (10) DE69435342D1 (un)
DK (5) DK0706376T4 (un)
ES (5) ES2290074T3 (un)
GR (1) GR3024833T3 (un)
HK (2) HK1042054B (un)
LU (2) LU92422I2 (un)
NO (2) NO324275B1 (un)
NZ (5) NZ511762A (un)
PT (4) PT1159974E (un)
RU (3) RU2180844C2 (un)
WO (1) WO1995003036A1 (un)

Cited By (115)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1995032722A1 (en) * 1994-04-28 1995-12-07 Les Laboratoires Aeterna Inc. Extracts of shark cartilage having an anti-angiogenic activity and an effect on tumor regression; process of making thereof
WO1996025176A1 (en) * 1995-02-15 1996-08-22 Neorx Corporation Therapeutic inhibitor of vascular smooth muscle cells
EP0734721A2 (en) * 1995-03-30 1996-10-02 Advanced Cardiovascular Systems, Inc. Method of incorporating drugs into a polymer component of stents
US5616608A (en) * 1993-07-29 1997-04-01 The United States Of America As Represented By The Department Of Health And Human Services Method of treating atherosclerosis or restenosis using microtubule stabilizing agent
WO1997045105A1 (en) * 1996-05-24 1997-12-04 Angiotech Pharmaceuticals, Inc. Compositions and methods for treating or preventing diseases of body passageways
WO1998000183A2 (en) * 1996-06-28 1998-01-08 Shaw, Robert, Francis Methods and compositions for the treatment and repair of defects or lesions in cartilage or bone using functional barrier
US5716981A (en) * 1993-07-19 1998-02-10 Angiogenesis Technologies, Inc. Anti-angiogenic compositions and methods of use
WO1999008729A1 (en) * 1997-08-13 1999-02-25 Boston Scientific Limited Loading and release of water-insoluble drugs
DE19744135C1 (de) * 1997-09-29 1999-03-25 Schering Ag Beschichtete medizinische Implantate, Verfahren zu ihrer Herstellung und ihre Verwendung zur Restenoseprophylaxe
EP0910301A1 (en) * 1996-06-12 1999-04-28 The Regents Of The University Of Michigan Compositions and methods for coating medical devices
WO1999044590A1 (en) * 1998-03-04 1999-09-10 Takeda Chemical Industries, Ltd. Sustained-release preparation for aii antagonist, production and use thereof
US5977163A (en) * 1996-03-12 1999-11-02 Pg-Txl Company, L. P. Water soluble paclitaxel prodrugs
US6025334A (en) * 1994-04-28 2000-02-15 Les Laboratoires Aeterna Inc. Extracts of shark cartilage having anti-collagenolytic, anti-inflammatory, anti-angiogenic and anti-tumoral activities; process of making, methods of using and compositions thereof
US6028118A (en) * 1996-08-08 2000-02-22 Les Laboratoires Aeterna Inc. Methods of using extracts of shark cartilage
WO2000010552A2 (en) * 1998-08-24 2000-03-02 Global Vascular Concepts, Inc. Use of anti-angiogenic agents for inhibiting vessel wall injury
WO2000021584A1 (en) * 1998-10-14 2000-04-20 Boston Scientific Limited Loading and release of water-insoluble drugs
WO2000032238A1 (en) * 1998-12-03 2000-06-08 Scimed Life Systems, Inc. Stent having drug crystals thereon
EP1010435A1 (en) * 1997-09-05 2000-06-21 Maruho K.K. Nanocapsule preparations for treating intraarticular diseases
WO2000050016A2 (en) * 1999-02-23 2000-08-31 Angiotech Pharmaceuticals, Inc. Compositions and methods for improving integrity of compromised body passageways and cavities
WO2000056283A1 (en) * 1999-03-24 2000-09-28 The B.F.Goodrich Company Inhibition of matrix metalloproteinases with polymers and pharmaceutical applications thereof
US6168807B1 (en) 1998-07-23 2001-01-02 Les Laboratoires Aeterna Inc. Low molecular weight components of shark cartilage, processes for their preparation and therapeutic uses thereof
WO2001036007A2 (en) * 1999-11-12 2001-05-25 Angiotech Pharmaceuticals, Inc. Compositions of a combination of radioactive therapy and cell-cycle inhibitors
US6380366B1 (en) 1994-04-28 2002-04-30 Les Laboratoires Aeterna Inc. Shark cartilage extract:process of making, methods of using and compositions thereof
US6383522B1 (en) 1997-03-11 2002-05-07 Les Laboratoires Aeterna, Inc. Toxicity reduced composition containing an anti-neoplastic agent and a shark cartilage extract
WO2002055121A1 (en) * 2001-01-11 2002-07-18 Biocompatibles Uk Limited Drug delivery from stents
US6441025B2 (en) 1996-03-12 2002-08-27 Pg-Txl Company, L.P. Water soluble paclitaxel derivatives
WO2002068000A2 (en) * 2000-11-16 2002-09-06 Microspherix Llc Polymeric imagable brachytherapy seed
US6485514B1 (en) 1997-12-12 2002-11-26 Supergen, Inc. Local delivery of therapeutic agents
WO2002094335A1 (en) * 2001-05-18 2002-11-28 Advanced Cardiovascular Systems, Inc. Medicated stents for the treatment of vascular disease
US6495579B1 (en) 1996-12-02 2002-12-17 Angiotech Pharmaceuticals, Inc. Method for treating multiple sclerosis
EP1278493A1 (en) * 1999-12-29 2003-01-29 Estrogen Vascular Technology, LLC Apparatus and method for delivering compounds to a living organism
US6515016B2 (en) 1996-12-02 2003-02-04 Angiotech Pharmaceuticals, Inc. Composition and methods of paclitaxel for treating psoriasis
WO2003089005A1 (fr) * 2002-04-22 2003-10-30 Reserach Foundation Itsuu Laboratory Medicaments de traitement de maladies vasculaires
US6730064B2 (en) 1998-08-20 2004-05-04 Cook Incorporated Coated implantable medical device
US6746661B2 (en) 2000-11-16 2004-06-08 Microspherix Llc Brachytherapy seed
US6774278B1 (en) 1995-06-07 2004-08-10 Cook Incorporated Coated implantable medical device
AU775787B2 (en) * 1996-05-24 2004-08-12 Angiotech Pharmaceuticals, Inc. Compositions and methods for treating or preventing diseases of body passageways
US6846841B2 (en) 1993-07-19 2005-01-25 Angiotech Pharmaceuticals, Inc. Anti-angiogenic compositions and methods of use
WO2005027951A1 (en) * 2003-09-16 2005-03-31 Glycogenesys, Inc. Method for controlling angiogenesis in animals
WO2006082221A1 (en) * 2005-02-03 2006-08-10 Cinvention Ag Drug delivery materials made by sol/gel technology
US7153864B2 (en) 2000-03-17 2006-12-26 Cell Therapeutics Inc. Polyglutamic acid-camptothecin conjugates and methods of preparation
EP1807018A2 (en) * 2004-10-21 2007-07-18 University of Iowa Research Foundation In situ controlled release drug delivery system
DE202008006190U1 (de) 2008-05-06 2008-07-17 Sellin, Lothar Restenoseprophylaxe
US7425217B2 (en) 2000-11-16 2008-09-16 Maier Nathan C System and method for inhibiting cellular proliferation with tachykinins
DE202008007347U1 (de) 2008-05-31 2008-10-16 Orlowski, Benjamin Daniel Kupfer Stent
CN100464736C (zh) * 2006-03-17 2009-03-04 山东蓝金生物工程有限公司 同载抗代谢药物及其增效剂的抗癌缓释注射剂
US7560112B2 (en) 2005-04-29 2009-07-14 Applied Molecular Evolution, Inc. Anti-il-6 antibodies, compositions, methods and uses
DE102008008263A1 (de) 2008-02-08 2009-08-13 Thomas Kuczera Restenoseprophylaxe
EP2098230A1 (en) 1997-03-31 2009-09-09 Boston Scientific Scimed Limited Use of cytoskeletal inhibitors in crystalline form for the inhibition or prevention of restenosis
DE102009059070A1 (de) 2008-12-19 2010-07-01 Lothar Sellin Medizinische Einrichtung und Verfahren zu ihrer Herstellung
US7750041B2 (en) 2001-03-26 2010-07-06 Bayer Schering Pharma Aktiengesellschaft Preparation for the prophylaxis of restenosis
US7758891B2 (en) 2005-02-18 2010-07-20 Abraxis Bioscience, Llc Combinations and modes of administration of therapeutic agents and combination therapy
US7771468B2 (en) 2001-03-16 2010-08-10 Angiotech Biocoatings Corp. Medicated stent having multi-layer polymer coating
EP1322235B2 (en) † 2000-09-29 2010-08-11 Cordis Corporation Coated medical devices
US7776310B2 (en) 2000-11-16 2010-08-17 Microspherix Llc Flexible and/or elastic brachytherapy seed or strand
US7819912B2 (en) 1998-03-30 2010-10-26 Innovational Holdings Llc Expandable medical device with beneficial agent delivery mechanism
US7820788B2 (en) 2002-12-09 2010-10-26 Abraxis Bioscience, Llc Compositions and methods of delivery of pharmacological agents
US7820193B2 (en) 1993-07-19 2010-10-26 Angiotech Pharmaceuticals, Inc. Anti-angiogenic compositions and methods of use
US7850728B2 (en) 2000-10-16 2010-12-14 Innovational Holdings Llc Expandable medical device for delivery of beneficial agent
US7862605B2 (en) 1995-06-07 2011-01-04 Med Institute, Inc. Coated implantable medical device
US7875677B2 (en) 2001-04-20 2011-01-25 The University Of British Columbia Micellar drug delivery systems for hydrophobic drugs
WO2009158724A3 (en) * 2008-06-27 2011-03-31 Tepha, Inc. Injectable delivery of microparticles and compos itions therefore
US7998105B2 (en) 1997-03-13 2011-08-16 Biocardia, Inc. Method of treating coronary arteries with perivascular delivery of therapeutic agents
US8096972B2 (en) 2000-08-30 2012-01-17 Johns Hopkins University Devices for intraocular drug delivery
US8097236B2 (en) 2001-02-22 2012-01-17 Psimedica Limited Devices and methods for the treatment of cancer
US8187321B2 (en) 2000-10-16 2012-05-29 Innovational Holdings, Llc Expandable medical device for delivery of beneficial agent
US8188235B2 (en) 2008-06-18 2012-05-29 Pfizer Inc. Antibodies to IL-6 and their uses
US8192483B2 (en) 2005-10-06 2012-06-05 Kaneka Corporation Stent to be placed in the living body
US8197881B2 (en) 2003-09-22 2012-06-12 Conor Medsystems, Inc. Method and apparatus for loading a beneficial agent into an expandable medical device
US8257305B2 (en) 2002-09-20 2012-09-04 Bayer Pharma Aktiengesellschaft Medical device for dispensing medicaments
US8313760B2 (en) 2002-05-24 2012-11-20 Angiotech International Ag Compositions and methods for coating medical implants
US8349390B2 (en) 2002-09-20 2013-01-08 Conor Medsystems, Inc. Method and apparatus for loading a beneficial agent into an expandable medical device
US8361537B2 (en) 1998-03-30 2013-01-29 Innovational Holdings, Llc Expandable medical device with beneficial agent concentration gradient
US8372420B2 (en) 2002-05-24 2013-02-12 Angiotech International Ag Compositions and methods for coating medical implants
US8512750B2 (en) 2001-01-11 2013-08-20 Abbott Laboratories Stents with drug-containing amphiphilic polymer coating
US8574604B2 (en) 2005-04-15 2013-11-05 Interface Biologics, Inc. Methods and compositions for the delivery of biologically active agents
US8591921B2 (en) 2008-04-10 2013-11-26 Virginia Commonwealth University Induction of tumor hypoxia for cancer therapy
US8632809B2 (en) 2006-11-09 2014-01-21 Alcon Research, Ltd. Water insoluble polymer matrix for drug delivery
US8691288B2 (en) 2006-05-10 2014-04-08 Medtronic, Inc. Gallium-containing sealant for medical use
US8734825B2 (en) 2008-09-15 2014-05-27 Covidien Lp Local delivery of water-soluble or water-insoluble therapeutic agents to the surface of body lumens
US8735394B2 (en) 2005-02-18 2014-05-27 Abraxis Bioscience, Llc Combinations and modes of administration of therapeutic agents and combination therapy
US8853260B2 (en) 1997-06-27 2014-10-07 Abraxis Bioscience, Llc Formulations of pharmacological agents, methods for the preparation thereof and methods for the use thereof
US8884027B2 (en) 2010-10-22 2014-11-11 University Of Rochester Melampomagnolide B derivatives as antileukemic and cytotoxic agents
US8883856B2 (en) * 2000-02-28 2014-11-11 John Jackson Compositions and methods for the treatment of inflammatory diseases using topoisomerase inhibitors
US8889211B2 (en) 2010-09-02 2014-11-18 Boston Scientific Scimed, Inc. Coating process for drug delivery balloons using heat-induced rewrap memory
US9034362B2 (en) 2008-09-15 2015-05-19 The Spectranetics Corporation Local delivery of water-soluble or water-insoluble therapeutic agents to the surface of body lumens
US9050393B2 (en) 2005-02-08 2015-06-09 Bruce N. Saffran Medical devices and methods for modulation of physiology using device-based surface chemistry
US9056152B2 (en) 2011-08-25 2015-06-16 Boston Scientific Scimed, Inc. Medical device with crystalline drug coating
US9119896B2 (en) 2007-02-08 2015-09-01 Medtronic Xomed, Inc. Polymeric sealant for medical use
DE202015002048U1 (de) 2015-03-16 2015-09-24 Han Bock-Sun Implantat
US9192697B2 (en) 2007-07-03 2015-11-24 Hemoteq Ag Balloon catheter for treating stenosis of body passages and for preventing threatening restenosis
US9198968B2 (en) 2008-09-15 2015-12-01 The Spectranetics Corporation Local delivery of water-soluble or water-insoluble therapeutic agents to the surface of body lumens
US9265836B2 (en) 2002-06-11 2016-02-23 Protherics Salt Lake City, Inc. Biodegradable block copolymeric compositions for drug delivery
US9283035B2 (en) 2005-04-28 2016-03-15 Boston Scientific Scimed, Inc. Tissue-treatment methods
US9308355B2 (en) 2012-06-01 2016-04-12 Surmodies, Inc. Apparatus and methods for coating medical devices
US9393318B2 (en) 2010-03-29 2016-07-19 Abraxis Bioscience, Llc Methods of treating cancer
US9399072B2 (en) 2010-06-04 2016-07-26 Abraxis Bioscience, Llc Methods of treatment of pancreatic cancer
US9463426B2 (en) 2005-06-24 2016-10-11 Boston Scientific Scimed, Inc. Methods and systems for coating particles
US9700344B2 (en) 2008-06-12 2017-07-11 Medtronic Xomed, Inc. Method for treating chronic wounds with an extracellular polymeric substance solvating system
US9827401B2 (en) 2012-06-01 2017-11-28 Surmodics, Inc. Apparatus and methods for coating medical devices
US9956385B2 (en) 2012-06-28 2018-05-01 The Spectranetics Corporation Post-processing of a medical device to control morphology and mechanical properties
US10080821B2 (en) 2009-07-17 2018-09-25 Boston Scientific Scimed, Inc. Nucleation of drug delivery balloons to provide improved crystal size and density
WO2019040335A1 (en) 2017-08-19 2019-02-28 University Of Rochester MICHELOLID DERIVATIVES, PREPARATION METHODS AND THEIR USE AS ANTICANCER AND ANTI-INFLAMMATORY AGENTS
RU2693042C2 (ru) * 2015-04-20 2019-07-01 Тгель Био Ко., Лтд. Набор для доставки лекарственного средства, и устройство, и способ, предназначенные для получения системы для доставки лекарственного средства
US10369256B2 (en) 2009-07-10 2019-08-06 Boston Scientific Scimed, Inc. Use of nanocrystals for drug delivery from a balloon
US10398724B2 (en) 2002-06-12 2019-09-03 Boston Scientific Scimed, Inc. Bulking agents
EP3359085A4 (en) * 2015-10-12 2019-09-18 Toth, Landy CONTROLLED AND PRECISE TREATMENT OF HEARTWOVEN
US10449162B2 (en) 2015-09-16 2019-10-22 Dfb Soria Llc Delivery of drug nanoparticles and methods of use thereof
US10525171B2 (en) 2014-01-24 2020-01-07 The Spectranetics Corporation Coatings for medical devices
US10555898B2 (en) 2017-03-15 2020-02-11 Dfb Soria, Llc Topical therapy for the treatment of skin malignancies using nanoparticles of taxanes
US10660965B2 (en) 2010-03-29 2020-05-26 Abraxis Bioscience, Llc Methods of enhancing drug delivery and effectiveness of therapeutic agents
US10842969B2 (en) 2013-10-25 2020-11-24 Mercator Medsystems, Inc. Systems and methods of treating malacia by local delivery of hydrogel to augment tissue
US11497726B2 (en) 2018-03-16 2022-11-15 Dfb Soria, Ll. Topical therapy for the treatment of cervical intraepithelial neoplasia (CIN) and cervical cancer using nanoparticles of taxanes
US11628466B2 (en) 2018-11-29 2023-04-18 Surmodics, Inc. Apparatus and methods for coating medical devices
US11819590B2 (en) 2019-05-13 2023-11-21 Surmodics, Inc. Apparatus and methods for coating medical devices

Families Citing this family (323)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5811447A (en) 1993-01-28 1998-09-22 Neorx Corporation Therapeutic inhibitor of vascular smooth muscle cells
US6558798B2 (en) 1995-02-22 2003-05-06 Scimed Life Systems, Inc. Hydrophilic coating and substrates coated therewith having enhanced durability and lubricity
US7846202B2 (en) * 1995-06-07 2010-12-07 Cook Incorporated Coated implantable medical device
US7896914B2 (en) * 1995-06-07 2011-03-01 Cook Incorporated Coated implantable medical device
US7867275B2 (en) * 1995-06-07 2011-01-11 Cook Incorporated Coated implantable medical device method
US7550005B2 (en) * 1995-06-07 2009-06-23 Cook Incorporated Coated implantable medical device
US20070203520A1 (en) * 1995-06-07 2007-08-30 Dennis Griffin Endovascular filter
ATE267587T1 (de) 1995-06-09 2004-06-15 Euro Celtique Sa Formulierungen und verfahren für eine verlängerte lokalanästhesie
JPH11511763A (ja) 1996-06-24 1999-10-12 ユーロ―セルティーク，エス．エイ． 安全な局所麻酔の提供方法
US7351421B2 (en) * 1996-11-05 2008-04-01 Hsing-Wen Sung Drug-eluting stent having collagen drug carrier chemically treated with genipin
US6204388B1 (en) * 1996-12-03 2001-03-20 Sloan-Kettering Institute For Cancer Research Synthesis of epothilones, intermediates thereto and analogues thereof
US6242469B1 (en) * 1996-12-03 2001-06-05 Sloan-Kettering Institute For Cancer Research Synthesis of epothilones, intermediates thereto, analogues and uses thereof
US20050043376A1 (en) * 1996-12-03 2005-02-24 Danishefsky Samuel J. Synthesis of epothilones, intermediates thereto, analogues and uses thereof
US6867305B2 (en) * 1996-12-03 2005-03-15 Sloan-Kettering Institute For Cancer Research Synthesis of epothilones, intermediates thereto and analogues thereof
US6273913B1 (en) * 1997-04-18 2001-08-14 Cordis Corporation Modified stent useful for delivery of drugs along stent strut
US20030199425A1 (en) * 1997-06-27 2003-10-23 Desai Neil P. Compositions and methods for treatment of hyperplasia
US7208011B2 (en) * 2001-08-20 2007-04-24 Conor Medsystems, Inc. Implantable medical device with drug filled holes
AU760408B2 (en) * 1998-04-27 2003-05-15 Surmodics, Inc. Bioactive agent release coating
US6293967B1 (en) 1998-10-29 2001-09-25 Conor Medsystems, Inc. Expandable medical device with ductile hinges
US6120847A (en) * 1999-01-08 2000-09-19 Scimed Life Systems, Inc. Surface treatment method for stent coating
US6419692B1 (en) 1999-02-03 2002-07-16 Scimed Life Systems, Inc. Surface protection method for stents and balloon catheters for drug delivery
US20020058286A1 (en) * 1999-02-24 2002-05-16 Danishefsky Samuel J. Synthesis of epothilones, intermediates thereto and analogues thereof
US6156373A (en) 1999-05-03 2000-12-05 Scimed Life Systems, Inc. Medical device coating methods and devices
US6290673B1 (en) * 1999-05-20 2001-09-18 Conor Medsystems, Inc. Expandable medical device delivery system and method
DE60018925T2 (de) * 1999-05-27 2006-04-13 Pharmacia Corp.(N.D.Ges.D.Staates Delaware) Biomaterialien, modifiziert mit superoxid-dismutase imitatoren
US20040110722A1 (en) * 1999-05-27 2004-06-10 Ornberg Richard L. Modified hyaluronic acid polymers
US6258121B1 (en) 1999-07-02 2001-07-10 Scimed Life Systems, Inc. Stent coating
DE29911689U1 (de) * 1999-07-06 2000-04-06 Sterk Peter Mittel für den Gefässverschluß von organischem Gewebe
US7687462B2 (en) 1999-10-05 2010-03-30 The Regents Of The University Of California Composition for promoting cartilage formation or repair comprising a nell gene product and method of treating cartilage-related conditions using such composition
DE60139112D1 (de) * 2000-03-06 2009-08-13 Boston Scient Ltd Unter ultralschall sichtbare embolisierende substanzen
ES2222352T3 (es) * 2000-03-18 2005-02-01 Polyzenix Gmbh Uso de derivados de polifosfaceno para recubrimientos antibacterianos.
WO2001072280A2 (en) * 2000-03-24 2001-10-04 Biosphere Medical Inc. Microspheres for gene therapy
US8697137B2 (en) 2000-03-24 2014-04-15 Biosphere Medical, Inc. Methods of using microspheres for active embolization
US20030212022A1 (en) * 2001-03-23 2003-11-13 Jean-Marie Vogel Compositions and methods for gene therapy
ATE350077T1 (de) 2000-04-11 2007-01-15 Polyzenix Gmbh Verwendung von folien aus poly-tri-fluor- ethoxypolyphosphazenen zur umhüllung von medizinischen vorrichtungen
EP1179353A1 (de) * 2000-08-11 2002-02-13 B. Braun Melsungen Ag Antithrombogene Implantate mit Beschichtung aus Polyphosphazenen und einem pharmakologisch aktiven Wirkstoff
US20090004240A1 (en) * 2000-08-11 2009-01-01 Celonova Biosciences, Inc. Implants with a phosphazene-containing coating
US7101391B2 (en) * 2000-09-18 2006-09-05 Inflow Dynamics Inc. Primarily niobium stent
US7402173B2 (en) * 2000-09-18 2008-07-22 Boston Scientific Scimed, Inc. Metal stent with surface layer of noble metal oxide and method of fabrication
US6764507B2 (en) 2000-10-16 2004-07-20 Conor Medsystems, Inc. Expandable medical device with improved spatial distribution
JP2004516051A (ja) 2000-11-21 2004-06-03 シエーリング アクチエンゲゼルシャフト 管状血管移植片（ステント）およびその製造法
DE10100961B4 (de) * 2001-01-11 2005-08-04 Polyzenix Gmbh Körperverträglicher Werkstoff und mit diesem Werkstoff beschichtetes Substrat für die Züchtung von Zellen und künstlichen aus Zellen aufgebauten oder gewachsenen organischen Implantaten
US9080146B2 (en) 2001-01-11 2015-07-14 Celonova Biosciences, Inc. Substrates containing polyphosphazene as matrices and substrates containing polyphosphazene with a micro-structured surface
US6685626B2 (en) 2001-02-02 2004-02-03 Regeneration Technologies, Inc. Compositions, devices, methods, and kits for induction of adhesions
US20020176893A1 (en) * 2001-02-02 2002-11-28 Wironen John F. Compositions, implants, methods, and kits for closure of lumen openings, repair of ruptured tissue, and for bulking of tissue
US6964680B2 (en) * 2001-02-05 2005-11-15 Conor Medsystems, Inc. Expandable medical device with tapered hinge
US20040204756A1 (en) * 2004-02-11 2004-10-14 Diaz Stephen Hunter Absorbent article with improved liquid acquisition capacity
WO2002072150A2 (en) * 2001-03-13 2002-09-19 Angiotech Pharmaceuticals Inc. Micellar drug delivery vehicles and uses thereof
US20040185101A1 (en) * 2001-03-27 2004-09-23 Macromed, Incorporated. Biodegradable triblock copolymers as solubilizing agents for drugs and method of use thereof
US20030157161A1 (en) * 2001-05-01 2003-08-21 Angiotech Pharmaceuticals, Inc. Compositions and methods for treating inflammatory conditions utilizing protein or polysaccharide containing anti-microtubule agents
US20030032935A1 (en) * 2001-08-10 2003-02-13 Scimed Life Systems, Inc. Packages facilitating convenient mixing and delivery of liquids
US20040253467A1 (en) * 2001-08-17 2004-12-16 Schuessler Andreas Device based on nitinol with a polyphosphazene coating
US7842083B2 (en) 2001-08-20 2010-11-30 Innovational Holdings, Llc. Expandable medical device with improved spatial distribution
US7056338B2 (en) * 2003-03-28 2006-06-06 Conor Medsystems, Inc. Therapeutic agent delivery device with controlled therapeutic agent release rates
US20040249443A1 (en) * 2001-08-20 2004-12-09 Shanley John F. Expandable medical device for treating cardiac arrhythmias
US7927368B2 (en) 2002-03-25 2011-04-19 Kieran Murphy Llc Device viewable under an imaging beam
US20030181810A1 (en) 2002-03-25 2003-09-25 Murphy Kieran P. Kit for image guided surgical procedures
US9375203B2 (en) 2002-03-25 2016-06-28 Kieran Murphy Llc Biopsy needle
US7131997B2 (en) * 2002-03-29 2006-11-07 Scimed Life Systems, Inc. Tissue treatment
US7462366B2 (en) 2002-03-29 2008-12-09 Boston Scientific Scimed, Inc. Drug delivery particle
US7094369B2 (en) * 2002-03-29 2006-08-22 Scimed Life Systems, Inc. Processes for manufacturing polymeric microspheres
US7053134B2 (en) * 2002-04-04 2006-05-30 Scimed Life Systems, Inc. Forming a chemically cross-linked particle of a desired shape and diameter
US20040038303A1 (en) * 2002-04-08 2004-02-26 Unger Gretchen M. Biologic modulations with nanoparticles
CZ294371B6 (cs) * 2002-06-10 2004-12-15 Pliva - Lachema, A. S. Stabilizovaná farmaceutická kompozice na bázi polyoxyethylovaného ricinového oleje a způsob její přípravy
US20030232087A1 (en) * 2002-06-18 2003-12-18 Lawin Laurie R. Bioactive agent release coating with aromatic poly(meth)acrylates
US7097850B2 (en) * 2002-06-18 2006-08-29 Surmodics, Inc. Bioactive agent release coating and controlled humidity method
CN100346850C (zh) * 2003-05-28 2007-11-07 微创医疗器械(上海)有限公司 一种药物涂层支架
US20080138433A1 (en) * 2002-07-05 2008-06-12 Celonova Biosciences, Inc. Vasodilator eluting blood storage and administration devices with a specific polyphosphazene coating and methods for their manufacture and use
US20080138377A1 (en) * 2002-07-05 2008-06-12 Celonova Biosciences, Inc. Vasodilator Eluting Luminal Stent Devices With A Specific Polyphosphazene Coating and Methods for Their Manufacture and Use
DK1521603T3 (da) 2002-07-12 2011-04-18 Cook Inc Coated medicinsk anordning
US20050163821A1 (en) * 2002-08-02 2005-07-28 Hsing-Wen Sung Drug-eluting Biodegradable Stent and Delivery Means
US7842377B2 (en) 2003-08-08 2010-11-30 Boston Scientific Scimed, Inc. Porous polymeric particle comprising polyvinyl alcohol and having interior to surface porosity-gradient
US20040076582A1 (en) * 2002-08-30 2004-04-22 Dimatteo Kristian Agent delivery particle
US7449236B2 (en) * 2002-08-09 2008-11-11 Boston Scientific Scimed, Inc. Porous polymeric particle comprising polyvinyl alcohol and having interior to surface porosity-gradient
US7649006B2 (en) * 2002-08-23 2010-01-19 Sloan-Kettering Institute For Cancer Research Synthesis of epothilones, intermediates thereto and analogues thereof
CA2496477C (en) 2002-08-23 2012-10-16 Sloan-Kettering Institute For Cancer Research Synthesis of epothilones, intermediates thereto, analogues and uses thereof
US6921769B2 (en) 2002-08-23 2005-07-26 Sloan-Kettering Institute For Cancer Research Synthesis of epothilones, intermediates thereto and analogues thereof
US8012454B2 (en) 2002-08-30 2011-09-06 Boston Scientific Scimed, Inc. Embolization
JP3887588B2 (ja) * 2002-08-30 2007-02-28 株式会社リガク Ｘ線回折による応力測定法
JP2006511475A (ja) * 2002-09-18 2006-04-06 トラスティーズ オブ ザ ユニバーシティ オブ ペンシルベニア 脈絡膜新生血管症の抑制方法
CA2499594A1 (en) * 2002-09-20 2004-04-01 Conor Medsystems, Inc. Expandable medical device with openings for delivery of multiple beneficial agents
US20040127976A1 (en) * 2002-09-20 2004-07-01 Conor Medsystems, Inc. Method and apparatus for loading a beneficial agent into an expandable medical device
CN1684725A (zh) * 2002-09-26 2005-10-19 血管技术国际股份公司 血管周包裹物
DE60310975T2 (de) * 2002-10-15 2007-07-12 Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical College Verwendung von epothilone zur behandlung hyperparathyreoidismus
AU2003286502A1 (en) * 2002-10-21 2004-05-13 The Government Of The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Contiguous capillary electrospray sources and analytical device
US7883490B2 (en) 2002-10-23 2011-02-08 Boston Scientific Scimed, Inc. Mixing and delivery of therapeutic compositions
US7588825B2 (en) * 2002-10-23 2009-09-15 Boston Scientific Scimed, Inc. Embolic compositions
US20040142014A1 (en) * 2002-11-08 2004-07-22 Conor Medsystems, Inc. Method and apparatus for reducing tissue damage after ischemic injury
JP2006505364A (ja) * 2002-11-08 2006-02-16 コナー　メドシステムズ，　インコーポレイテッド 血管新生因子の局所供給を用いる、慢性全梗塞を処置するための拡張可能な医療装置および方法
KR20130032407A (ko) * 2002-11-08 2013-04-01 코너 메드시스템즈, 엘엘씨 허혈성 상해 후에 조직 손상을 감소시키기 위한 방법 및 장치
US20060121080A1 (en) 2002-11-13 2006-06-08 Lye Whye K Medical devices having nanoporous layers and methods for making the same
JP2006514848A (ja) 2002-11-13 2006-05-18 セタゴン インコーポレーティッド 多孔質層を有する医療装置およびその作製方法
US9770349B2 (en) 2002-11-13 2017-09-26 University Of Virginia Patent Foundation Nanoporous stents with enhanced cellular adhesion and reduced neointimal formation
US7338557B1 (en) * 2002-12-17 2008-03-04 Advanced Cardiovascular Systems, Inc. Nozzle for use in coating a stent
US7842791B2 (en) 2002-12-19 2010-11-30 Nancy Jean Britten Dispersible pharmaceutical compositions
ES2355727T3 (es) * 2003-03-26 2011-03-30 Celonova Biosciences Germany Gmbh Implantes dentales recubiertos.
EP2289571B1 (en) 2003-03-28 2016-08-03 Innovational Holdings, LLC Implantable medical device with beneficial agent concentration gradient
JP2006523235A (ja) * 2003-03-28 2006-10-12 コーザン バイオサイエンシス インコーポレイテッド 再狭窄を予防するための装置、方法及び組成物
US20040202692A1 (en) * 2003-03-28 2004-10-14 Conor Medsystems, Inc. Implantable medical device and method for in situ selective modulation of agent delivery
US20050010170A1 (en) * 2004-02-11 2005-01-13 Shanley John F Implantable medical device with beneficial agent concentration gradient
US7306580B2 (en) 2003-04-16 2007-12-11 Cook Incorporated Medical device with therapeutic agents
US20040220534A1 (en) * 2003-04-29 2004-11-04 Martens Paul W. Medical device with antimicrobial layer
EP1633320A2 (en) * 2003-05-02 2006-03-15 SurModics, Inc. Implantable controlled release bioactive agent delivery device
US8246974B2 (en) * 2003-05-02 2012-08-21 Surmodics, Inc. Medical devices and methods for producing the same
US7169179B2 (en) * 2003-06-05 2007-01-30 Conor Medsystems, Inc. Drug delivery device and method for bi-directional drug delivery
US20050064005A1 (en) * 2003-08-13 2005-03-24 Dinh Thomas Q. Active agent delivery systems including a miscible polymer blend, medical devices, and methods
WO2005018600A2 (en) * 2003-08-22 2005-03-03 Cube Medical A/S Method of treating a patient suffering from a solid tumour
US7976823B2 (en) 2003-08-29 2011-07-12 Boston Scientific Scimed, Inc. Ferromagnetic particles and methods
US7585517B2 (en) * 2003-09-18 2009-09-08 Macusight, Inc. Transscleral delivery
US7056337B2 (en) * 2003-10-21 2006-06-06 Cook Incorporated Natural tissue stent
US7901770B2 (en) 2003-11-04 2011-03-08 Boston Scientific Scimed, Inc. Embolic compositions
US20050100529A1 (en) * 2003-11-06 2005-05-12 Zeldis Jerome B. Methods of using and compositions comprising immunomodulatory compounds for the treatment and management of asbestos-related diseases and disorders
FR2861993B1 (fr) * 2003-11-06 2006-01-21 Jean Claude Rigaud Complexe moleculaire anti restenose pour endoprothese intracoronaire
US20050100577A1 (en) * 2003-11-10 2005-05-12 Parker Theodore L. Expandable medical device with beneficial agent matrix formed by a multi solvent system
CA2536042A1 (en) * 2003-11-10 2005-06-02 Angiotech International Ag Medical implants and anti-scarring agents
US20050208095A1 (en) * 2003-11-20 2005-09-22 Angiotech International Ag Polymer compositions and methods for their use
CA2536242A1 (en) * 2003-11-20 2005-06-09 Angiotech International Ag Implantable sensors and implantable pumps and anti-scarring agents
US20050209664A1 (en) * 2003-11-20 2005-09-22 Angiotech International Ag Electrical devices and anti-scarring agents
JP2007519756A (ja) * 2004-01-30 2007-07-19 アンジオテック インターナショナル アーゲー 拘縮を治療するための組成物および方法
US7349971B2 (en) * 2004-02-05 2008-03-25 Scenera Technologies, Llc System for transmitting data utilizing multiple communication applications simultaneously in response to user request without specifying recipient's communication information
US7294145B2 (en) * 2004-02-26 2007-11-13 Boston Scientific Scimed, Inc. Stent with differently coated inside and outside surfaces
US7736671B2 (en) 2004-03-02 2010-06-15 Boston Scientific Scimed, Inc. Embolization
US8173176B2 (en) 2004-03-30 2012-05-08 Boston Scientific Scimed, Inc. Embolization
US8003122B2 (en) * 2004-03-31 2011-08-23 Cordis Corporation Device for local and/or regional delivery employing liquid formulations of therapeutic agents
WO2005099786A1 (en) * 2004-04-06 2005-10-27 Surmodics, Inc. Coating compositions for bioactive agents
US20060083772A1 (en) * 2004-04-06 2006-04-20 Dewitt David M Coating compositions for bioactive agents
US20050238870A1 (en) * 2004-04-22 2005-10-27 Marcia Buiser Embolization
DE602004007630T2 (de) * 2004-05-25 2008-06-05 William Cook Europe Aps Stent und Stentbeseitigungsvorrichtung
US7311861B2 (en) 2004-06-01 2007-12-25 Boston Scientific Scimed, Inc. Embolization
US20050287287A1 (en) * 2004-06-24 2005-12-29 Parker Theodore L Methods and systems for loading an implantable medical device with beneficial agent
WO2006004774A2 (en) * 2004-06-28 2006-01-12 Stanford University Laulimalide analogues as therapeutic agents
US8236338B2 (en) 2004-07-13 2012-08-07 The University Of Tennessee Research Foundation Adhesive composition for carrying therapeutic agents as delivery vehicle on coatings applied to vascular grafts
US8119153B2 (en) * 2004-08-26 2012-02-21 Boston Scientific Scimed, Inc. Stents with drug eluting coatings
EP1799151A4 (en) * 2004-09-15 2014-09-17 Conor Medsystems Inc BINDERSTAND WITH A CERPRINCIBLE END AND METHOD FOR STORING A STENT IN A BIFURCATION
US20210299056A9 (en) 2004-10-25 2021-09-30 Varian Medical Systems, Inc. Color-Coded Polymeric Particles of Predetermined Size for Therapeutic and/or Diagnostic Applications and Related Methods
US9107850B2 (en) 2004-10-25 2015-08-18 Celonova Biosciences, Inc. Color-coded and sized loadable polymeric particles for therapeutic and/or diagnostic applications and methods of preparing and using the same
US9114162B2 (en) 2004-10-25 2015-08-25 Celonova Biosciences, Inc. Loadable polymeric particles for enhanced imaging in clinical applications and methods of preparing and using the same
US20060093647A1 (en) * 2004-10-29 2006-05-04 Villafana Manuel A Multiple layer coating composition
ES2424255T3 (es) * 2004-11-08 2013-09-30 Baxter International Inc. Composiciones particuladas de inhibidores de tubulina
US8425550B2 (en) 2004-12-01 2013-04-23 Boston Scientific Scimed, Inc. Embolic coils
EP1845951B1 (en) * 2005-01-28 2010-09-15 Tepha, Inc. Embolization using poly-4-hydroxybutyrate particles
US8663639B2 (en) 2005-02-09 2014-03-04 Santen Pharmaceutical Co., Ltd. Formulations for treating ocular diseases and conditions
SI1848431T1 (sl) * 2005-02-09 2016-05-31 Santen Pharmaceutical Co., Ltd. Tekoče formulacije za zdravljenje bolezni ali stanj
AU2005100176A4 (en) * 2005-03-01 2005-04-07 Gym Tv Pty Ltd Garbage bin clip
US7858183B2 (en) 2005-03-02 2010-12-28 Boston Scientific Scimed, Inc. Particles
US7727555B2 (en) 2005-03-02 2010-06-01 Boston Scientific Scimed, Inc. Particles
US20060224170A1 (en) * 2005-03-30 2006-10-05 Michael Duff Surgical marker clip and method for cholangiography
KR101429774B1 (ko) 2005-05-09 2014-10-02 바이오스피어 메디칼 에스.에이. 마이크로스피어 및 비이온성 조영제를 사용하는 조성물 및방법
US20060280787A1 (en) * 2005-06-14 2006-12-14 Baxter International Inc. Pharmaceutical formulation of the tubulin inhibitor indibulin for oral administration with improved pharmacokinetic properties, and process for the manufacture thereof
US20070004973A1 (en) * 2005-06-15 2007-01-04 Tan Sharon M L Tissue treatment methods
US20060286071A1 (en) * 2005-06-21 2006-12-21 Epstein Samuel J Therapeutic pastes for medical device coating
US7736293B2 (en) 2005-07-22 2010-06-15 Biocompatibles Uk Limited Implants for use in brachytherapy and other radiation therapy that resist migration and rotation
US8187159B2 (en) 2005-07-22 2012-05-29 Biocompatibles, UK Therapeutic member including a rail used in brachytherapy and other radiation therapy
CA2618404A1 (en) * 2005-08-04 2007-02-15 Angiotech International Ag Block copolymer compositions and uses thereof
TR200801336T1 (tr) 2005-08-31 2008-08-21 Abraxis Bioscience, Inc. Kararlılığı artmış zayıf su çöznurluğune sahip ilaçların preparasyonuna yönelik kompozisyonlar ve yöntemler.
AU2006284657B2 (en) * 2005-08-31 2012-07-19 Abraxis Bioscience, Llc Compositions and methods for preparation of poorly water soluble drugs with increased stability
US8007509B2 (en) 2005-10-12 2011-08-30 Boston Scientific Scimed, Inc. Coil assemblies, components and methods
US8101197B2 (en) 2005-12-19 2012-01-24 Stryker Corporation Forming coils
US8152839B2 (en) 2005-12-19 2012-04-10 Boston Scientific Scimed, Inc. Embolic coils
US7947368B2 (en) 2005-12-21 2011-05-24 Boston Scientific Scimed, Inc. Block copolymer particles
US7501179B2 (en) * 2005-12-21 2009-03-10 Boston Scientific Scimed, Inc. Block copolymer particles
JP5528708B2 (ja) 2006-02-09 2014-06-25 参天製薬株式会社 安定な製剤ならびにそれらを調製および使用する方法
US8222271B2 (en) * 2006-03-23 2012-07-17 Santen Pharmaceutical Co., Ltd. Formulations and methods for vascular permeability-related diseases or conditions
JP2009538317A (ja) * 2006-05-26 2009-11-05 バイエル ヘルスケア リミティド ライアビリティ カンパニー 癌治療のための置換ジアリールウレアを用いた薬物の組み合わせ
US20070298069A1 (en) * 2006-06-26 2007-12-27 Boston Scientific Scimed, Inc. Medical devices for release of low solubility therapeutic agents
US9023075B2 (en) * 2006-06-30 2015-05-05 Cvdevices, Llc Devices, systems, and methods for lead delivery
WO2008134245A1 (en) * 2007-04-27 2008-11-06 Cvdevices, Llc Devices, systems, and methods for promotion of infarct healing and reinforcement of border zone
JP2009542338A (ja) * 2006-06-30 2009-12-03 シーヴィ デヴァイシズ，エルエルシー 心臓組織への経皮的血管内アクセス
US20080051702A1 (en) * 2006-08-24 2008-02-28 Herrmann Robert A Therapeutic agent delivery for the treatment of asthma via implantable and insertable medical devices
EP2099506A2 (en) * 2006-10-10 2009-09-16 Celonova Biosciences Inc. Compositions and devices comrising silicone and specific polyphosphazenes
JP2010505597A (ja) 2006-10-10 2010-02-25 セロノバ バイオサイエンシーズ， インコーポレイテッド ポリホスファゼンを用いたバイオ人工心臓弁
US20080167592A1 (en) * 2006-10-26 2008-07-10 Greer Steven E Preventing or treating wounds with a collodion barrier incorporating active agents
US8414927B2 (en) 2006-11-03 2013-04-09 Boston Scientific Scimed, Inc. Cross-linked polymer particles
CN101553207B (zh) * 2006-11-09 2013-01-16 爱尔康研究有限公司 包含水不溶性聚合物基质的泪点塞
US8414526B2 (en) 2006-11-20 2013-04-09 Lutonix, Inc. Medical device rapid drug releasing coatings comprising oils, fatty acids, and/or lipids
US9737640B2 (en) 2006-11-20 2017-08-22 Lutonix, Inc. Drug releasing coatings for medical devices
US20080276935A1 (en) 2006-11-20 2008-11-13 Lixiao Wang Treatment of asthma and chronic obstructive pulmonary disease with anti-proliferate and anti-inflammatory drugs
US9700704B2 (en) 2006-11-20 2017-07-11 Lutonix, Inc. Drug releasing coatings for balloon catheters
US20080175887A1 (en) 2006-11-20 2008-07-24 Lixiao Wang Treatment of Asthma and Chronic Obstructive Pulmonary Disease With Anti-proliferate and Anti-inflammatory Drugs
US8998846B2 (en) 2006-11-20 2015-04-07 Lutonix, Inc. Drug releasing coatings for balloon catheters
US8414910B2 (en) 2006-11-20 2013-04-09 Lutonix, Inc. Drug releasing coatings for medical devices
US8430055B2 (en) 2008-08-29 2013-04-30 Lutonix, Inc. Methods and apparatuses for coating balloon catheters
US8414525B2 (en) 2006-11-20 2013-04-09 Lutonix, Inc. Drug releasing coatings for medical devices
US8425459B2 (en) 2006-11-20 2013-04-23 Lutonix, Inc. Medical device rapid drug releasing coatings comprising a therapeutic agent and a contrast agent
US20080171068A1 (en) * 2007-01-17 2008-07-17 Etcetera Llc Antimicrobial, infection-control and odor-control film and film composite
DE102007003184A1 (de) 2007-01-22 2008-07-24 Orlowski, Michael, Dr. Verfahren zur Beladung von strukturierten Oberflächen
EP2125058B1 (en) * 2007-02-07 2014-12-03 Cook Medical Technologies LLC Medical device coatings for releasing a therapeutic agent at multiple rates
US20100076489A1 (en) * 2007-03-06 2010-03-25 Joshua Stopek Wound closure material
US9888924B2 (en) * 2007-03-06 2018-02-13 Covidien Lp Wound closure material
CA2678889A1 (en) * 2007-03-06 2008-09-12 Tyco Healthcare Group Lp Wound closure material
US8781193B2 (en) 2007-03-08 2014-07-15 Sync-Rx, Ltd. Automatic quantitative vessel analysis
US10716528B2 (en) 2007-03-08 2020-07-21 Sync-Rx, Ltd. Automatic display of previously-acquired endoluminal images
US11197651B2 (en) 2007-03-08 2021-12-14 Sync-Rx, Ltd. Identification and presentation of device-to-vessel relative motion
US11064964B2 (en) 2007-03-08 2021-07-20 Sync-Rx, Ltd Determining a characteristic of a lumen by measuring velocity of a contrast agent
US9375164B2 (en) 2007-03-08 2016-06-28 Sync-Rx, Ltd. Co-use of endoluminal data and extraluminal imaging
US9305334B2 (en) 2007-03-08 2016-04-05 Sync-Rx, Ltd. Luminal background cleaning
US9968256B2 (en) 2007-03-08 2018-05-15 Sync-Rx Ltd. Automatic identification of a tool
WO2008107905A2 (en) 2007-03-08 2008-09-12 Sync-Rx, Ltd. Imaging and tools for use with moving organs
US9629571B2 (en) 2007-03-08 2017-04-25 Sync-Rx, Ltd. Co-use of endoluminal data and extraluminal imaging
US20080265343A1 (en) * 2007-04-26 2008-10-30 International Business Machines Corporation Field effect transistor with inverted t shaped gate electrode and methods for fabrication thereof
US9050064B2 (en) * 2007-04-27 2015-06-09 Cvdevices, Llc Systems for engaging a bodily tissue and methods of using the same
EP2144569A4 (en) * 2007-04-27 2014-03-26 Cvdevices Llc DEVICES, SYSTEMS AND METHODS OF ACCESSING THE EPICARDIAL HEART SURFACE
JP5174891B2 (ja) 2007-04-27 2013-04-03 シーヴィ デヴァイシズ，エルエルシー 心臓の心外膜表面にアクセスするための装置、システム、および方法
US8540674B2 (en) 2007-04-27 2013-09-24 Cvdevices, Llc Devices, systems, and methods for transeptal atrial puncture using an engagement catheter platform
CN101801521B (zh) 2007-05-14 2015-06-17 纽约州立大学研究基金会 生物膜中细菌细胞内的生理学分散响应诱导
US8147769B1 (en) 2007-05-16 2012-04-03 Abbott Cardiovascular Systems Inc. Stent and delivery system with reduced chemical degradation
JP2008305262A (ja) * 2007-06-08 2008-12-18 Konica Minolta Business Technologies Inc サーバ及びシンクライアント環境でのプリンタ紹介方法
EP2207570A2 (en) * 2007-09-14 2010-07-21 Nitto Denko Corporation Drug carriers
EP2050441A1 (en) * 2007-10-19 2009-04-22 Université Victor Segalen Bordeaux 2 Use of beta blocker for the manufacture of a medicament for the treatment of hemangiomas
FR2922452B1 (fr) * 2007-10-19 2010-01-22 Coatex Sas Formulations de composes organoplatiniques en presence de polymeres associatifs, produits obtenus et leurs utilisations
US20090110730A1 (en) * 2007-10-30 2009-04-30 Celonova Biosciences, Inc. Loadable Polymeric Particles for Marking or Masking Individuals and Methods of Preparing and Using the Same
EP2249909A4 (en) * 2008-02-05 2013-06-19 Cvdevices Llc CATHETER DEVICES WITH GUIDING COMMITMENT, SYSTEMS AND METHODS
US8365432B2 (en) * 2008-03-19 2013-02-05 Morimoto-Pharma Co., Ltd. Freeze-drying method and freeze-drying apparatus
US20090319031A1 (en) * 2008-06-19 2009-12-24 Yunbing Wang Bioabsorbable Polymeric Stent With Improved Structural And Molecular Weight Integrity
EP2310063B1 (en) * 2008-07-03 2016-09-28 Vesseltek Biomedical, LLC Controlled and localized release of retinoids to improve neointimal hyperplasia
US8128951B2 (en) 2008-09-15 2012-03-06 Cv Ingenuity Corp. Local delivery of water-soluble or water-insoluble therapeutic agents to the surface of body lumens
US20100070013A1 (en) * 2008-09-18 2010-03-18 Medtronic Vascular, Inc. Medical Device With Microsphere Drug Delivery System
US8076529B2 (en) 2008-09-26 2011-12-13 Abbott Cardiovascular Systems, Inc. Expandable member formed of a fibrous matrix for intraluminal drug delivery
US8500687B2 (en) 2008-09-25 2013-08-06 Abbott Cardiovascular Systems Inc. Stent delivery system having a fibrous matrix covering with improved stent retention
US8049061B2 (en) 2008-09-25 2011-11-01 Abbott Cardiovascular Systems, Inc. Expandable member formed of a fibrous matrix having hydrogel polymer for intraluminal drug delivery
US8226603B2 (en) 2008-09-25 2012-07-24 Abbott Cardiovascular Systems Inc. Expandable member having a covering formed of a fibrous matrix for intraluminal drug delivery
US9186128B2 (en) 2008-10-01 2015-11-17 Covidien Lp Needle biopsy device
US9782565B2 (en) 2008-10-01 2017-10-10 Covidien Lp Endoscopic ultrasound-guided biliary access system
US9332973B2 (en) 2008-10-01 2016-05-10 Covidien Lp Needle biopsy device with exchangeable needle and integrated needle protection
US11298113B2 (en) 2008-10-01 2022-04-12 Covidien Lp Device for needle biopsy with integrated needle protection
US8968210B2 (en) 2008-10-01 2015-03-03 Covidien LLP Device for needle biopsy with integrated needle protection
US9974509B2 (en) 2008-11-18 2018-05-22 Sync-Rx Ltd. Image super enhancement
US9101286B2 (en) 2008-11-18 2015-08-11 Sync-Rx, Ltd. Apparatus and methods for determining a dimension of a portion of a stack of endoluminal data points
US9144394B2 (en) 2008-11-18 2015-09-29 Sync-Rx, Ltd. Apparatus and methods for determining a plurality of local calibration factors for an image
US10362962B2 (en) 2008-11-18 2019-07-30 Synx-Rx, Ltd. Accounting for skipped imaging locations during movement of an endoluminal imaging probe
US8855744B2 (en) 2008-11-18 2014-10-07 Sync-Rx, Ltd. Displaying a device within an endoluminal image stack
US9095313B2 (en) 2008-11-18 2015-08-04 Sync-Rx, Ltd. Accounting for non-uniform longitudinal motion during movement of an endoluminal imaging probe
US11064903B2 (en) 2008-11-18 2021-07-20 Sync-Rx, Ltd Apparatus and methods for mapping a sequence of images to a roadmap image
EP2210584A1 (en) * 2009-01-27 2010-07-28 Bayer Schering Pharma Aktiengesellschaft Stable polymeric composition comprising an epothilone and an amphiphilic block copolymer
WO2010093945A2 (en) 2009-02-13 2010-08-19 Glaukos Corporation Uveoscleral drug delivery implant and methods for implanting the same
JP4782850B2 (ja) * 2009-02-24 2011-09-28 シャープ株式会社 画像データ処理装置
US7828996B1 (en) 2009-03-27 2010-11-09 Abbott Cardiovascular Systems Inc. Method for the manufacture of stable, nano-sized particles
WO2010117668A1 (en) * 2009-03-30 2010-10-14 Cerulean Pharma Inc. Polymer-agent conjugates, particles, compositions, and related methods of use
WO2010114770A1 (en) * 2009-03-30 2010-10-07 Cerulean Pharma Inc. Polymer-agent conjugates, particles, compositions, and related methods of use
WO2010114768A1 (en) * 2009-03-30 2010-10-07 Cerulean Pharma Inc. Polymer-epothilone conjugates, particles, compositions, and related methods of use
EP2243501A1 (en) 2009-04-24 2010-10-27 Eurocor Gmbh Shellac and paclitaxel coated catheter balloons
CA2760187C (en) 2009-04-28 2018-01-02 Ralph A. Chappa Devices and methods for delivery of bioactive agents
DE202009006632U1 (de) 2009-05-07 2009-07-16 Sellin, Lothar Beschichtung von medizinischen Oberflächen
US20100285085A1 (en) * 2009-05-07 2010-11-11 Abbott Cardiovascular Systems Inc. Balloon coating with drug transfer control via coating thickness
WO2012071476A2 (en) 2010-11-24 2012-05-31 David Haffner Drug eluting ocular implant
US10206813B2 (en) 2009-05-18 2019-02-19 Dose Medical Corporation Implants with controlled drug delivery features and methods of using same
US20110319987A1 (en) 2009-05-20 2011-12-29 Arsenal Medical Medical implant
US9309347B2 (en) 2009-05-20 2016-04-12 Biomedical, Inc. Bioresorbable thermoset polyester/urethane elastomers
AU2010249558A1 (en) * 2009-05-20 2011-12-08 Arsenal Medical, Inc. Medical implant
US8888840B2 (en) * 2009-05-20 2014-11-18 Boston Scientific Scimed, Inc. Drug eluting medical implant
US9265633B2 (en) 2009-05-20 2016-02-23 480 Biomedical, Inc. Drug-eluting medical implants
US8992601B2 (en) 2009-05-20 2015-03-31 480 Biomedical, Inc. Medical implants
US8372133B2 (en) * 2009-10-05 2013-02-12 480 Biomedical, Inc. Polymeric implant delivery system
US8945508B2 (en) 2009-10-13 2015-02-03 The Regents Of The University Of Michigan Dendrimer compositions and methods of synthesis
DE202009014776U1 (de) 2009-11-02 2010-03-11 Sellin, Lothar Beschichtung
CN102695500A (zh) 2009-11-09 2012-09-26 聚光灯技术合伙有限责任公司 多糖基水凝胶
AU2010314994B2 (en) 2009-11-09 2016-10-06 Spotlight Technology Partners Llc Fragmented hydrogels
JP2013514278A (ja) 2009-12-18 2013-04-25 インターフェース バイオロジクス，インコーポレーテッド 自己集合コーティングからの薬物の局所送達
DE202009017490U1 (de) 2009-12-22 2010-04-08 Sellin, Lothar Weihrauch- und/oder Boswelliasäuren Beschichtung
US20110218606A1 (en) * 2010-03-02 2011-09-08 Medtronic Vascular, Inc. Methods for Stabilizing Femoral Vessels
US20110224720A1 (en) * 2010-03-11 2011-09-15 Cvdevices, Llc Devices, systems, and methods for closing a hole in cardiac tissue
US10413506B2 (en) 2010-04-03 2019-09-17 Praful Doshi Medical devices including medicaments and methods of making and using same including enhancing comfort, enhancing drug penetration, and treatment of myopia
WO2011133183A1 (en) * 2010-04-20 2011-10-27 University Of Utah Research Foundation Phase separation sprayed scaffold
CA2798084A1 (en) 2010-05-17 2011-11-24 Aerie Pharmaceuticals, Inc. Drug delivery devices for delivery of ocular therapeutic agents
US8858577B2 (en) 2010-05-19 2014-10-14 University Of Utah Research Foundation Tissue stabilization system
US8945156B2 (en) 2010-05-19 2015-02-03 University Of Utah Research Foundation Tissue fixation
SG186109A1 (en) * 2010-06-02 2013-01-30 Abraxis Bioscience Llc Methods of treating bladder cancer
WO2012073627A1 (ja) 2010-12-02 2012-06-07 丸善製薬株式会社 Ｔｉｅ２活性化剤、血管内皮増殖因子（ＶＥＧＦ）阻害剤、血管新生抑制剤、血管の成熟化剤、血管の正常化剤、及び血管の安定化剤、並びに医薬品組成物
CN103458903B (zh) * 2011-01-28 2017-07-04 Abk生物医学公司 不透射线的栓塞颗粒
US8852214B2 (en) 2011-02-04 2014-10-07 University Of Utah Research Foundation System for tissue fixation to bone
DE202011002713U1 (de) 2011-02-14 2011-04-14 Sellin, Lothar Biologisch abbaubare medizinische Beschichtung und deren Verwendung
US10213529B2 (en) 2011-05-20 2019-02-26 Surmodics, Inc. Delivery of coated hydrophobic active agent particles
US9757497B2 (en) 2011-05-20 2017-09-12 Surmodics, Inc. Delivery of coated hydrophobic active agent particles
US9861727B2 (en) 2011-05-20 2018-01-09 Surmodics, Inc. Delivery of hydrophobic active agent particles
US10245178B1 (en) 2011-06-07 2019-04-02 Glaukos Corporation Anterior chamber drug-eluting ocular implant
RU2467705C1 (ru) * 2011-06-30 2012-11-27 ФЕДЕРАЛЬНОЕ ГОСУДАРСТВЕННОЕ УЧРЕЖДЕНИЕ "РОССИЙСКИЙ НАУЧНЫЙ ЦЕНТР РАДИОЛОГИИ И ХИРУРГИЧЕСКИХ ТЕХНОЛОГИЙ" МИНИСТЕРСТВА ЗДРАВООХРАНЕНИЯ И СОЦИАЛЬНОГО РАЗВИТИЯ РОССИЙСКОЙ ФЕДЕРАЦИИ (ФГУ "РНЦРХТ" Минздравсоцразвития России) Способ лечения облитерирующего атеросклероза сосудов нижних конечностей
EP2574918B1 (de) 2011-09-28 2014-12-10 Mems Ag Mikrothermisches Verfahren und Sensor zur Bestimmung physikalischer Gaseigenschaften
DE202011106744U1 (de) 2011-10-15 2011-11-11 Lothar Sellin Bessere Bioverfügbarkeit von Shellac/Paclitaxel Beschichtungen
US20130197657A1 (en) * 2011-12-08 2013-08-01 Diana Anca Central airway stent
US20130245759A1 (en) * 2012-03-09 2013-09-19 The Florida International University Board Of Trustees Medical devices incorporating silicone nanoparticles, and uses thereof
EP2852319B1 (en) * 2012-05-21 2017-05-17 Sync-RX, Ltd. Co-use of endoluminal data and extraluminal imaging
US20130317622A1 (en) * 2012-05-25 2013-11-28 Antonio Sambusseti Surgical method for grafting an artificial implant in a bladder and/or in a urethral or ureteral segment
JP6134789B2 (ja) 2012-06-26 2017-05-24 シンク−アールエックス，リミティド 管腔器官における流れに関連する画像処理
WO2014008875A1 (de) 2012-07-12 2014-01-16 Cardionovum Gmbh Katheterballon, verfahren zur herstellung eines beschichteten katheterballons sowie verwendung des pharmakologischen wirkstoffs
US10390935B2 (en) 2012-07-30 2019-08-27 Conextions, Inc. Soft tissue to bone repair devices, systems, and methods
US11944531B2 (en) 2012-07-30 2024-04-02 Conextions, Inc. Devices, systems, and methods for repairing soft tissue and attaching soft tissue to bone
US10835241B2 (en) 2012-07-30 2020-11-17 Conextions, Inc. Devices, systems, and methods for repairing soft tissue and attaching soft tissue to bone
US10219804B2 (en) 2012-07-30 2019-03-05 Conextions, Inc. Devices, systems, and methods for repairing soft tissue and attaching soft tissue to bone
US9427309B2 (en) 2012-07-30 2016-08-30 Conextions, Inc. Soft tissue repair devices, systems, and methods
US11957334B2 (en) 2012-07-30 2024-04-16 Conextions, Inc. Devices, systems, and methods for repairing soft tissue and attaching soft tissue to bone
US11253252B2 (en) 2012-07-30 2022-02-22 Conextions, Inc. Devices, systems, and methods for repairing soft tissue and attaching soft tissue to bone
EP2912121B1 (en) 2012-10-29 2019-09-25 Ariste Medical, LLC Polymer coating compositions and coated products
US11246963B2 (en) 2012-11-05 2022-02-15 Surmodics, Inc. Compositions and methods for delivery of hydrophobic active agents
WO2014071387A1 (en) 2012-11-05 2014-05-08 Surmodics, Inc. Composition and method for delivery of hydrophobic active agents
RU2528249C2 (ru) * 2012-11-23 2014-09-10 Федеральное государственное бюджетное образовательное учреждение высшего профессионального образования "Московский государственный университет имени М.В. Ломоносова" (МГУ) Способ подавления ангиогенеза с помощью рекомбинантных форм урокиназы
US20140212355A1 (en) * 2013-01-28 2014-07-31 Abbott Cardiovascular Systems Inc. Trans-arterial drug delivery
CA2907009A1 (en) * 2013-03-15 2014-09-18 Microtech Medical Technologies Ltd. Implantable anchor
DE202013002567U1 (de) 2013-03-18 2013-05-07 Lothar Sellin NABP - Beschichtung
CN105188666A (zh) 2013-04-01 2015-12-23 阿勒根公司 用于持续的眼内释放的微球药物递送系统
US20150119850A1 (en) * 2013-10-25 2015-04-30 Mercator Medsystems, Inc. Maintenance of Bronchial Patency by Local Delivery of Cytotoxic, Cytostatic, or Anti-Neoplastic Agent
US11583384B2 (en) 2014-03-12 2023-02-21 Conextions, Inc. Devices, systems, and methods for repairing soft tissue and attaching soft tissue to bone
WO2015138760A1 (en) 2014-03-12 2015-09-17 Conextions, Inc. Soft tissue repair devices, systems, and methods
AU2015231110B2 (en) 2014-03-21 2019-03-07 University Of Pittsburgh - Of The Commonwealth System Of Higher Education Methods for preparation of a terminally sterilized hydrogel derived from extracellular matrix
EP3134482B1 (en) 2014-04-22 2020-06-03 Ariste Medical, LLC Methods and processes for application of drug delivery polymeric coatings
WO2015184173A1 (en) 2014-05-29 2015-12-03 Dose Medical Corporation Implants with controlled drug delivery features and methods of using same
RU2555378C1 (ru) * 2014-07-10 2015-07-10 Вадим Викторович Евдокимов Способ эндоскопической остановки и профилактики язвенных кровотечений из дефектов стенки 12-перстной кишки
WO2016036960A1 (en) 2014-09-03 2016-03-10 Genesegues, Inc. Therapeutic nanoparticles and related compositions, methods and systems
CA2968129C (en) 2014-11-26 2023-11-07 Abk Biomedical Inc. Radioembolic particles
WO2016093412A1 (ko) * 2014-12-10 2016-06-16 주식회사 에이치제이메디칼 경동맥 화학색전술에 적용되는 인산염완충용액(PBS) 또는 인산버퍼(Phosphate Buffer)가 함유된 젤라틴 스폰지 및 이의 제조방법
CN107847447A (zh) * 2015-06-18 2018-03-27 灵敏生物公司 可植入的药物递送组合物及其使用方法
KR101748120B1 (ko) * 2015-07-13 2017-06-16 서울대학교산학협력단 나노입자-유리체 기반 단백질 복합체를 유효성분으로 포함하는 혈관신생억제용 조성물 및 이의 용도
US11925578B2 (en) 2015-09-02 2024-03-12 Glaukos Corporation Drug delivery implants with bi-directional delivery capacity
US11564833B2 (en) 2015-09-25 2023-01-31 Glaukos Corporation Punctal implants with controlled drug delivery features and methods of using same
CN108699522B (zh) 2016-01-13 2022-05-27 高等教育联邦系统-匹兹堡大学 血管细胞外基质水凝胶
CN109937025B (zh) 2016-04-20 2022-07-29 多斯医学公司 生物可吸收眼部药物的递送装置
US11696822B2 (en) 2016-09-28 2023-07-11 Conextions, Inc. Devices, systems, and methods for repairing soft tissue and attaching soft tissue to bone
US10898446B2 (en) 2016-12-20 2021-01-26 Surmodics, Inc. Delivery of hydrophobic active agents from hydrophilic polyether block amide copolymer surfaces
US11547397B2 (en) 2017-12-20 2023-01-10 Conextions, Inc. Devices, systems, and methods for repairing soft tissue and attaching soft tissue to bone
CA3091800A1 (en) 2018-02-20 2019-08-29 Conextions, Inc. Devices, systems, and methods for repairing soft tissue and attaching soft tissue to bone
EP3796948A4 (en) 2018-05-22 2022-03-02 Interface Biologics Inc. COMPOSITIONS AND METHODS FOR ADMINISTRATION OF MEDICATIONS TO A VESSEL WALL
CN109224119B (zh) * 2018-10-30 2021-02-23 北京大学深圳医院 一种π共轭纳米自组装颗粒瘤内注射栓塞肿瘤血管抗癌剂
CN111388757B (zh) * 2020-03-21 2022-07-15 哈尔滨工程大学 一种采用螺旋镁丝制备的可降解镁基复合材料
AU2021400746A1 (en) 2020-12-17 2023-07-06 Mobius Therapeutics, Llc Injection apparatus and method of use

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0375520A1 (fr) * 1988-12-20 1990-06-27 Centre International De Recherches Dermatologiques Galderma - Cird Galderma Composition cosmétique ou pharmaceutique contenant des microsphères de polymères ou de corps gras chargées d'au moins un produit actif
WO1991010424A1 (en) * 1990-01-12 1991-07-25 Northwestern University Method of inhibiting angiogenesis of tumors
WO1991011193A1 (en) * 1990-01-25 1991-08-08 Children's Hospital Method and compositions for inhibiting angiogenesis
EP0470569A1 (en) * 1990-08-08 1992-02-12 Takeda Chemical Industries, Ltd. Intravascular embolizing agent containing angiogenesis inhibiting substance
WO1992012717A2 (en) * 1991-01-15 1992-08-06 A composition containing a tetracycline and use for inhibiting angiogenesis
WO1992015286A1 (en) * 1991-02-27 1992-09-17 Nova Pharmaceutical Corporation Anti-infective and anti-inflammatory releasing systems for medical devices
EP0567816A1 (de) * 1992-04-30 1993-11-03 BEHRINGWERKE Aktiengesellschaft Verwendung von Inhibitoren von Plasminogenaktivatoren zur Behandlung von Entzündungen und Wunden

Family Cites Families (242)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3016308A (en) * 1957-08-06 1962-01-09 Moore Business Forms Inc Recording paper coated with microscopic capsules of coloring material, capsules and method of making
US3029188A (en) 1958-02-20 1962-04-10 Olin Mathieson Gelatin adhesive pharmaceutical preparations
US3991527A (en) 1975-07-10 1976-11-16 Bates Abrasive Products, Inc. Coated abrasive disc
USRE30239E (en) 1975-11-10 1980-03-25 Cell proliferation and tissue invasion inhibitor
US4042457A (en) 1975-11-10 1977-08-16 Rush-Presbyterian-St. Luke's Medical Center Preparation of tissue invasion inhibitor and method of treatment utilizing the inhibitor
US4391797A (en) 1977-01-05 1983-07-05 The Children's Hospital Medical Center Systems for the controlled release of macromolecules
US4176177A (en) 1978-11-16 1979-11-27 Rush-Presbyterian-St. Luke's Medical Center Inhibition of bone resorption
US4416877A (en) 1979-02-13 1983-11-22 Symphar S.A. Anti-atherosclerotic pharmaceutical compositions containing diphosphonate compounds
US4300244A (en) 1979-09-19 1981-11-17 Carbomedics, Inc. Cardiovascular grafts
US4356261A (en) 1980-04-22 1982-10-26 Rush-Presbyterian-St. Luke's Medical Center Anti-invasion factor containing cultures
US4531936A (en) * 1981-01-29 1985-07-30 Gordon Robert T Device and method for the selective delivery of drugs to the myocardium
US4768523A (en) 1981-04-29 1988-09-06 Lifecore Biomedical, Inc. Hydrogel adhesive
US4357312A (en) 1981-07-16 1982-11-02 The Children's Hospital Medical Center Method of making prolonged release body
US4534899A (en) * 1981-07-20 1985-08-13 Lipid Specialties, Inc. Synthetic phospholipid compounds
US5441745A (en) 1982-03-30 1995-08-15 Vestar, Inc. Method of delivering micellular particles encapsulating chemotherapeutic agents to tumors in a body
US4542025A (en) 1982-07-29 1985-09-17 The Stolle Research And Development Corporation Injectable, long-acting microparticle formulation for the delivery of anti-inflammatory agents
US5001116A (en) 1982-12-20 1991-03-19 The Children's Medical Center Corporation Inhibition of angiogenesis
US4994443A (en) 1982-12-20 1991-02-19 The Children's Medical Center Corporation Inhibition of angiogenesis
US4906474A (en) 1983-03-22 1990-03-06 Massachusetts Institute Of Technology Bioerodible polyanhydrides for controlled drug delivery
US5286763A (en) 1983-03-22 1994-02-15 Massachusetts Institute Of Technology Bioerodible polymers for drug delivery in bone
US4834755A (en) * 1983-04-04 1989-05-30 Pfizer Hospital Products Group, Inc. Triaxially-braided fabric prosthesis
US4959358A (en) 1983-06-06 1990-09-25 Beth Israel Hospital Assn. Drug administration
US4500676A (en) 1983-12-15 1985-02-19 Biomatrix, Inc. Hyaluronate modified polymeric articles
GB8334484D0 (en) 1983-12-24 1984-02-01 Smith & Nephew Ass Surgical dressing
US4591496A (en) 1984-01-16 1986-05-27 Massachusetts Institute Of Technology Process for making systems for the controlled release of macromolecules
CA1295796C (en) 1984-03-27 1992-02-18 Conrad Whyne Biodegradable matrix and methods for producing same
US4779806A (en) 1984-07-23 1988-10-25 Massachusetts Institute Of Technology Ultrasonically modulated polymeric devices for delivering compositions
US4580568A (en) * 1984-10-01 1986-04-08 Cook, Incorporated Percutaneous endovascular stent and method for insertion thereof
US4789501A (en) 1984-11-19 1988-12-06 The Curators Of The University Of Missouri Glass microspheres
US5128326A (en) 1984-12-06 1992-07-07 Biomatrix, Inc. Drug delivery systems based on hyaluronans derivatives thereof and their salts and methods of producing same
US4916219A (en) 1985-03-28 1990-04-10 University Of Iowa Research Foundation Oligosaccharide heparin fragments as inhibitors of complement cascade
US4824436A (en) * 1985-04-09 1989-04-25 Harvey Wolinsky Method for the prevention of restenosis
US5102417A (en) * 1985-11-07 1992-04-07 Expandable Grafts Partnership Expandable intraluminal graft, and method and apparatus for implanting an expandable intraluminal graft
US4733665C2 (en) * 1985-11-07 2002-01-29 Expandable Grafts Partnership Expandable intraluminal graft and method and apparatus for implanting an expandable intraluminal graft
US4771042A (en) 1985-11-25 1988-09-13 The Upjohn Company Inhibition of angiogenesis involving the coadministration of steroids with heparin or heparin fragments
GB8601100D0 (en) 1986-01-17 1986-02-19 Cosmas Damian Ltd Drug delivery system
US4806621A (en) 1986-01-21 1989-02-21 Massachusetts Institute Of Technology Biocompatible, bioerodible, hydrophobic, implantable polyimino carbonate article
EP0556940A1 (en) * 1986-02-24 1993-08-25 Robert E. Fischell Intravascular stent
US4966890A (en) 1986-04-04 1990-10-30 Angiogenics, Ltd. Method and composition for arresting angiogenesis and capillary, cell or membrane leakage
US4955878A (en) * 1986-04-04 1990-09-11 Biotechnology, Inc. Kit for preventing or treating arterial dysfunction resulting from angioplasty procedures
US4746729A (en) 1986-07-30 1988-05-24 Kuettner Klaus E Cartilage-derived leukocyte elastase-inhibitor
US4882168A (en) 1986-09-05 1989-11-21 American Cyanamid Company Polyesters containing alkylene oxide blocks as drug delivery systems
GB2194885A (en) 1986-09-10 1988-03-23 Ephraim Kaplan Pharmaceutical compositions containing vanadium
US4893623A (en) 1986-12-09 1990-01-16 Advanced Surgical Intervention, Inc. Method and apparatus for treating hypertrophy of the prostate gland
CH673117A5 (un) 1986-12-10 1990-02-15 Ajinomoto Kk
US5092885A (en) * 1987-02-12 1992-03-03 The Government Of The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Peptides with laminin activity
US5084441A (en) 1987-03-04 1992-01-28 Shaw Jack M Acetylated low density lipoproteins: a delivery system to phagocytic cells for stimulating immunologic response and host resistance
US4800882A (en) * 1987-03-13 1989-01-31 Cook Incorporated Endovascular stent and delivery system
US5041126A (en) 1987-03-13 1991-08-20 Cook Incorporated Endovascular stent and delivery system
US4861627A (en) 1987-05-01 1989-08-29 Massachusetts Institute Of Technology Preparation of multiwall polymeric microcapsules
US4808402A (en) 1987-05-29 1989-02-28 Northwestern University Method and compositions for modulating neovascularization
NL8701337A (nl) 1987-06-09 1989-01-02 Sentron V O F Substraat voorzien van een bloedcompatibel oppervlak, verkregen door koppeling aan het oppervlak van een fysiologisch aktieve stof met remmende invloed op de vorming van bloedstolsels en/of in staat om gevormde bloedstolsels af te breken, alsmede werkwijze ter vervaardiging van het substraat.
US5059211A (en) * 1987-06-25 1991-10-22 Duke University Absorbable vascular stent
US4829099A (en) 1987-07-17 1989-05-09 Bioresearch, Inc. Metabolically acceptable polyisocyanate adhesives
US5019379A (en) 1987-07-31 1991-05-28 Massachusetts Institute Of Technology Unsaturated polyanhydrides
GB8720440D0 (en) 1987-08-28 1987-10-07 Smith & Nephew Ass Curable compositions
US5001009A (en) 1987-09-02 1991-03-19 Sterilization Technical Services, Inc. Lubricious hydrophilic composite coated on substrates
US5059189A (en) 1987-09-08 1991-10-22 E. R. Squibb & Sons, Inc. Method of preparing adhesive dressings containing a pharmaceutically active ingredient
US4983395A (en) 1987-11-12 1991-01-08 Theratech Inc. Device for administering an active agent to the skin or mucosa
US5135919A (en) * 1988-01-19 1992-08-04 Children's Medical Center Corporation Method and a pharmaceutical composition for the inhibition of angiogenesis
JP2995069B2 (ja) * 1988-01-19 1999-12-27 フォークマン，モーゼス，ジューダ 生長阻害剤およびその使用
US5460817A (en) 1988-01-19 1995-10-24 Allied Colloids Ltd. Particulate composition comprising a core of matrix polymer with active ingredient distributed therein
US5446070A (en) 1991-02-27 1995-08-29 Nover Pharmaceuticals, Inc. Compositions and methods for topical administration of pharmaceutically active agents
US4942184A (en) 1988-03-07 1990-07-17 The United States Of America As Represented By The Department Of Health And Human Services Water soluble, antineoplastic derivatives of taxol
US5157049A (en) * 1988-03-07 1992-10-20 The United States Of America As Represented By The Department Of Health & Human Services Method of treating cancers sensitive to treatment with water soluble derivatives of taxol
JPH0722576B2 (ja) 1988-04-11 1995-03-15 三菱電機株式会社 磁気共鳴装置
US4989601A (en) * 1988-05-02 1991-02-05 Medical Engineering & Development Institute, Inc. Method, apparatus, and substance for treating tissue having neoplastic cells
JP3038339B2 (ja) 1988-05-02 2000-05-08 ザイナクシス・テクノロジーズ・インコーポレーテッド バイオ粒子の表面膜に対してバイオアフェクティング物質を結合する化合物
US5096892A (en) 1988-05-27 1992-03-17 The Children's Medical Center Corporation Arylsulfatase inhibition and potentiation of angiostatic steroids and heparin
US5100668A (en) 1988-06-14 1992-03-31 Massachusetts Institute Of Technology Controlled release systems containing heparin and growth factors
JPH0643336B2 (ja) 1988-06-30 1994-06-08 呉羽化学工業株式会社 血管増殖抑制剤
DE3825374A1 (de) * 1988-07-26 1990-02-01 Schwendener Reto Dipl Apotheke Komplex aus mindestens einer lipophilen saeure und mitoxantron und/oder bisantren
US4966605A (en) 1988-07-28 1990-10-30 Thieler William R Method for opening and closing surgical wounds
JPH0255064A (ja) * 1988-08-03 1990-02-23 Toa O カテーテルを用いた血管内血栓の血栓除去装置
US5213580A (en) * 1988-08-24 1993-05-25 Endoluminal Therapeutics, Inc. Biodegradable polymeric endoluminal sealing process
US5019090A (en) * 1988-09-01 1991-05-28 Corvita Corporation Radially expandable endoprosthesis and the like
US5053048A (en) * 1988-09-22 1991-10-01 Cordis Corporation Thromboresistant coating
US5252713A (en) * 1988-09-23 1993-10-12 Neorx Corporation Polymeric carriers for non-covalent drug conjugation
US4938763B1 (en) 1988-10-03 1995-07-04 Atrix Lab Inc Biodegradable in-situ forming implants and method of producing the same
US5091176A (en) 1988-11-02 1992-02-25 W. R. Grace & Co.-Conn. Polymer-modified peptide drugs having enhanced biological and pharmacological activities
US5211657A (en) * 1988-11-07 1993-05-18 The United States Government As Represented By The Secretary Of The Department Of Health And Human Services Laminin a chain deduced amino acid sequence, expression vectors and active synthetic peptides
US5086164A (en) 1989-01-10 1992-02-04 Repligen Corporation Novel methods and compositions for treatment of angiogenic diseases
US5356630A (en) 1989-02-22 1994-10-18 Massachusetts Institute Of Technology Delivery system for controlled release of bioactive factors
US4960790A (en) 1989-03-09 1990-10-02 University Of Kansas Derivatives of taxol, pharmaceutical compositions thereof and methods for the preparation thereof
US4905694A (en) 1989-04-04 1990-03-06 Ethicon, Inc. Intracorporeal temporary wound closure
WO1990013332A1 (en) * 1989-05-11 1990-11-15 Cedars-Sinai Medical Center Stent with sustained drug delivery
AU648505B2 (en) * 1989-05-19 1994-04-28 Amgen, Inc. Metalloproteinase inhibitor
US4990155A (en) * 1989-05-19 1991-02-05 Wilkoff Howard M Surgical stent method and apparatus
US5132315A (en) 1989-05-19 1992-07-21 The United States Of America As Represented By The Department Of Health And Human Services Therapeutic application of an anti-invasive compound
US5171262A (en) 1989-06-15 1992-12-15 Cordis Corporation Non-woven endoprosthesis
CA2015946A1 (en) * 1989-06-27 1990-12-27 Lawrence P. Klemann Diol lipid analogues as edible fat replacements
US5290807A (en) 1989-08-10 1994-03-01 Children's Medical Center Corporation Method for regressing angiogenesis using o-substituted fumagillol derivatives
EP0415294A3 (en) 1989-08-31 1991-06-12 Takeda Chemical Industries, Ltd. Cyclohexanol derivatives, production and use thereof
CA1340994C (en) * 1989-09-21 2000-05-16 Rudolf Edgar Dr. Falk Treatment of conditions and disease
JPH03109324A (ja) 1989-09-22 1991-05-09 Microbial Chem Res Found 血管新生阻害剤
US5461081A (en) 1989-09-28 1995-10-24 Alcon Laboratories, Inc. Topical ophthalmic pharmaceutical vehicles
US5525348A (en) 1989-11-02 1996-06-11 Sts Biopolymers, Inc. Coating compositions comprising pharmaceutical agents
US5120548A (en) 1989-11-07 1992-06-09 Merck & Co., Inc. Swelling modulated polymeric drug delivery device
WO1991007154A1 (en) 1989-11-13 1991-05-30 President And Fellows Of Harvard College EXTRALUMINAL REGULATION OF THE GROWTH AND REPAIR OF TUBULAR STRUCTURES ιIN VIVO
US5527532A (en) 1989-11-13 1996-06-18 President And Fellows Of Harvard College Extraluminal regulation of the growth and repair of tubular structures in vivo
US5176617A (en) * 1989-12-11 1993-01-05 Medical Innovative Technologies R & D Limited Partnership Use of a stent with the capability to inhibit malignant growth in a vessel such as a biliary duct
US5059166A (en) * 1989-12-11 1991-10-22 Medical Innovative Technologies R & D Limited Partnership Intra-arterial stent with the capability to inhibit intimal hyperplasia
US5304121A (en) * 1990-12-28 1994-04-19 Boston Scientific Corporation Drug delivery system making use of a hydrogel polymer coating
US5439446A (en) * 1994-06-30 1995-08-08 Boston Scientific Corporation Stent and therapeutic delivery system
US5049132A (en) * 1990-01-08 1991-09-17 Cordis Corporation Balloon catheter for delivering therapeutic agents
ATE120377T1 (de) 1990-02-08 1995-04-15 Howmedica Aufblasbarer dilatator.
US5075112A (en) 1990-02-12 1991-12-24 Cartilage Technologies Inc. Method of and dosage unit for inhibiting angiogenesis or vascularization in an animal using shark cartilage
US5200397A (en) 1990-02-22 1993-04-06 W. R. Grace & Co.-Conn. Use of peptide analogs of thrombospondin for the inhibition of angiogenic activity
US5545208A (en) * 1990-02-28 1996-08-13 Medtronic, Inc. Intralumenal drug eluting prosthesis
EP0470246B1 (en) 1990-02-28 1995-06-28 Medtronic, Inc. Intralumenal drug eluting prosthesis
DE4006609A1 (de) 1990-03-02 1991-09-26 Max Planck Gesellschaft Inhibitor der proliferation von endothelzellen
US5052998A (en) 1990-04-04 1991-10-01 Zimmon David S Indwelling stent and method of use
DE69131574T2 (de) 1990-05-14 2000-05-04 Gary R Jernberg Chirurgisches implantat und verfahren zum einbetten von chemotherapeutika
US5219564A (en) 1990-07-06 1993-06-15 Enzon, Inc. Poly(alkylene oxide) amino acid copolymers and drug carriers and charged copolymers based thereon
US5290271A (en) * 1990-05-14 1994-03-01 Jernberg Gary R Surgical implant and method for controlled release of chemotherapeutic agents
US5092841A (en) * 1990-05-17 1992-03-03 Wayne State University Method for treating an arterial wall injured during angioplasty
WO1991017724A1 (en) * 1990-05-17 1991-11-28 Harbor Medical Devices, Inc. Medical device polymer
US5407683A (en) 1990-06-01 1995-04-18 Research Corporation Technologies, Inc. Pharmaceutical solutions and emulsions containing taxol
DE69110467T2 (de) * 1990-06-15 1996-02-01 Cortrak Medical Inc Vorrichtung zur abgabe von medikamenten.
US5462751A (en) 1990-06-22 1995-10-31 The Regeants Of The University Of California Biological and pharmaceutical agents having a nanomeric biodegradable core
US5064435A (en) 1990-06-28 1991-11-12 Schneider (Usa) Inc. Self-expanding prosthesis having stable axial length
JP3120187B2 (ja) * 1990-08-08 2000-12-25 武田薬品工業株式会社 血管新生阻害物質を含む血管内塞栓剤
US5210155A (en) * 1990-08-24 1993-05-11 Exxon Chemical Patents Inc. Phenol terminated diester compositions derived from dicarboxylic acids, polyester polymers or alkyd polymers, and curable compositions containing same
US5278324A (en) 1990-08-28 1994-01-11 Virginia Tech Intellectual Properties, Inc. Water soluble derivatives of taxol
NO302481B1 (no) 1990-10-16 1998-03-09 Takeda Chemical Industries Ltd Polymer for et preparat med forlenget frigjöring, samt preparat med forlenget frigjöring
WO1992006701A1 (en) 1990-10-18 1992-04-30 Huffstutler, M., Conrad, Jr. Preparation of concentrated fluid symphytum extracts, therapeutic forms and methods of use
DE69116130T2 (de) * 1990-10-18 1996-05-15 Ho Young Song Selbstexpandierender, endovaskulärer dilatator
EP0558751B1 (en) 1990-11-20 2000-02-02 Kowa Co. Ltd. Therapeutic agent for the treatment of wounds
US5268384A (en) 1990-11-21 1993-12-07 Galardy Richard E Inhibition of angiogenesis by synthetic matrix metalloprotease inhibitors
JP2928892B2 (ja) 1990-11-27 1999-08-03 三洋化成工業株式会社 外科用接着剤
US5149368A (en) 1991-01-10 1992-09-22 Liu Sung Tsuen Resorbable bioactive calcium phosphate cement
US5540928A (en) 1991-02-27 1996-07-30 President And Fellows Of Harvard College Extraluminal regulation of the growth and repair of tubular structures in vivo
US5171217A (en) 1991-02-28 1992-12-15 Indiana University Foundation Method for delivery of smooth muscle cell inhibitors
KR0177492B1 (ko) * 1991-03-08 1999-05-01 케이지 이가키 맥관 스텐트, 맥관 스텐트 유지 구조체 및 맥관 스텐트 삽입 고착장치
IT1250421B (it) 1991-05-30 1995-04-07 Recordati Chem Pharm Composizione farmaceutica a rilascio controllato con proprieta' bio-adesive.
US5147370A (en) 1991-06-12 1992-09-15 Mcnamara Thomas O Nitinol stent for hollow body conduits
US5330768A (en) 1991-07-05 1994-07-19 Massachusetts Institute Of Technology Controlled drug delivery using polymer/pluronic blends
FR2678833B1 (fr) 1991-07-08 1995-04-07 Rhone Poulenc Rorer Sa Nouvelles compositions pharmaceutiques a base de derives de la classe des taxanes.
US5344644A (en) 1991-08-01 1994-09-06 Takeda Chemical Industries, Ltd. Water-soluble composition for sustained-release
JPH0558882A (ja) * 1991-09-04 1993-03-09 Yoshiaki Kawashima ナノカプセルの製造法
US5229526A (en) 1991-09-23 1993-07-20 Florida State University Metal alkoxides
US5283253A (en) 1991-09-23 1994-02-01 Florida State University Furyl or thienyl carbonyl substituted taxanes and pharmaceutical compositions containing them
US6515009B1 (en) 1991-09-27 2003-02-04 Neorx Corporation Therapeutic inhibitor of vascular smooth muscle cells
US5811447A (en) 1993-01-28 1998-09-22 Neorx Corporation Therapeutic inhibitor of vascular smooth muscle cells
WO1993006792A1 (en) * 1991-10-04 1993-04-15 Scimed Life Systems, Inc. Biodegradable drug delivery vascular stent
US5464450A (en) 1991-10-04 1995-11-07 Scimed Lifesystems Inc. Biodegradable drug delivery vascular stent
CA2380683C (en) * 1991-10-28 2006-08-08 Advanced Cardiovascular Systems, Inc. Expandable stents and method for making same
US5318780A (en) 1991-10-30 1994-06-07 Mediventures Inc. Medical uses of in situ formed gels
JPH05131753A (ja) * 1991-11-15 1993-05-28 Fujicopian Co Ltd 多数回使用可能な熱転写インクシート
US5302397A (en) 1991-11-19 1994-04-12 Amsden Brian G Polymer-based drug delivery system
US5270047A (en) * 1991-11-21 1993-12-14 Kauffman Raymond F Local delivery of dipyridamole for the treatment of proliferative diseases
AU3140093A (en) 1991-11-22 1993-06-15 University Of Mississippi, The Synthesis and optical resolution of the taxol side chain and related compounds
CA2124329C (en) † 1991-11-27 2008-11-18 Gregory A. Kopia Compounds, compositions and methods for binding bio-affecting substances to surface membranes of bio-particles
US5260002A (en) 1991-12-23 1993-11-09 Vanderbilt University Method and apparatus for producing uniform polymeric spheres
CA2086642C (en) 1992-01-09 2004-06-15 Randall E. Morris Method of treating hyperproliferative vascular disease
US5516781A (en) 1992-01-09 1996-05-14 American Home Products Corporation Method of treating restenosis with rapamycin
US5176626A (en) 1992-01-15 1993-01-05 Wilson-Cook Medical, Inc. Indwelling stent
US5260066A (en) 1992-01-16 1993-11-09 Srchem Incorporated Cryogel bandage containing therapeutic agent
US6080777A (en) 1992-01-31 2000-06-27 The Trustees Of Columbia University In The City Of New York Taxol as a radiation sensitizer
US5301664A (en) 1992-03-06 1994-04-12 Sievers Robert E Methods and apparatus for drug delivery using supercritical solutions
US5200534A (en) 1992-03-13 1993-04-06 University Of Florida Process for the preparation of taxol and 10-deacetyltaxol
DE69326631T2 (de) 1992-03-19 2000-06-08 Medtronic Inc Intraluminales Erweiterungsgerät
US5474765A (en) * 1992-03-23 1995-12-12 Ut Sw Medical Ctr At Dallas Preparation and use of steroid-polyanionic polymer-based conjugates targeted to vascular endothelial cells
ES2148223T3 (es) 1992-03-23 2000-10-16 Univ Georgetown Taxol encapsulado en liposomas y metodo para su uso.
AU670937B2 (en) 1992-04-28 1996-08-08 Wyeth Method of treating hyperproliferative vascular disease
US5461140A (en) 1992-04-30 1995-10-24 Pharmaceutical Delivery Systems Bioerodible polymers for solid controlled release pharmaceutical compositions
AU4373993A (en) * 1992-05-14 1993-12-13 Ohio State University Research Foundation, The Treatment of vascular leakage syndrome and collagenase induced disease by administration of matrix metalloproteinase inhibitors
AU4242993A (en) 1992-05-21 1993-12-13 Penn State Research Foundation, The Cultured (taxus) tissues as a source of taxol, related taxanes and other novel anti-tumor/anti-viral compounds
WO1993024476A1 (en) 1992-06-04 1993-12-09 Clover Consolidated, Limited Water-soluble polymeric carriers for drug delivery
US5383928A (en) * 1992-06-10 1995-01-24 Emory University Stent sheath for local drug delivery
GB9213077D0 (en) 1992-06-19 1992-08-05 Erba Carlo Spa Polymerbound taxol derivatives
US5274137A (en) 1992-06-23 1993-12-28 Nicolaou K C Intermediates for preparation of taxols
US5294637A (en) 1992-07-01 1994-03-15 Bristol-Myers Squibb Company Fluoro taxols
US5273965A (en) 1992-07-02 1993-12-28 Cambridge Biotech Corporation Methods for enhancing drug delivery with modified saponins
FR2693193B1 (fr) * 1992-07-03 1994-09-02 Rhone Poulenc Rorer Sa Nouveaux dérivés de la désacétyl-10 baccatine III, leur préparation et les compositions pharmaceutiques qui les contiennent.
US5472954A (en) 1992-07-14 1995-12-05 Cyclops H.F. Cyclodextrin complexation
KR940003548U (ko) 1992-08-14 1994-02-21 김형술 세탁물 건조기
US5202448A (en) 1992-08-14 1993-04-13 Napro Biotherapeutics, Inc. Processes of converting taxanes into baccatin III
WO1994005282A1 (en) 1992-09-04 1994-03-17 The Scripps Research Institute Water soluble taxol derivatives
US5342621A (en) * 1992-09-15 1994-08-30 Advanced Cardiovascular Systems, Inc. Antithrombogenic surface
US5770609A (en) 1993-01-28 1998-06-23 Neorx Corporation Prevention and treatment of cardiovascular pathologies
CA2145093C (en) 1992-09-25 2007-04-10 Lawrence Leroy Kunz Therapeutic inhibitor of vascular smooth muscle cells
US6306421B1 (en) * 1992-09-25 2001-10-23 Neorx Corporation Therapeutic inhibitor of vascular smooth muscle cells
CA2100808A1 (en) 1992-10-01 1994-04-02 Vittorio Farina Deoxy paclitaxels
FR2696461B1 (fr) 1992-10-05 1994-11-10 Rhone Poulenc Rorer Sa Nouveaux dérivés d'analogues du taxol, leur préparation et les compositions qui les contiennent.
FR2696463B1 (fr) 1992-10-05 1994-11-25 Rhone Poulenc Rorer Sa Procédé d'obtention de la désacétyl-10 baccatine III.
FR2696462B1 (fr) 1992-10-05 1994-11-25 Rhone Poulenc Rorer Sa Procédé d'obtention de la désacétyl-10 baccatine III.
FR2696464B1 (fr) 1992-10-05 1994-11-10 Rhone Poulenc Rorer Sa Nouveau procédé d'estérification de la baccatine III et de la désacétyl-10 baccatine III.
FR2698543B1 (fr) 1992-12-02 1994-12-30 Rhone Poulenc Rorer Sa Nouvelles compositions à base de taxoides.
US5380751A (en) 1992-12-04 1995-01-10 Bristol-Myers Squibb Company 6,7-modified paclitaxels
US5342348A (en) * 1992-12-04 1994-08-30 Kaplan Aaron V Method and device for treating and enlarging body lumens
US5279949A (en) 1992-12-07 1994-01-18 Board Of Trustees Operating Michigan State University Process for the isolation and purification of taxol and taxanes from Taxus spp
EP0604022A1 (en) 1992-12-22 1994-06-29 Advanced Cardiovascular Systems, Inc. Multilayered biodegradable stent and method for its manufacture
US5419760A (en) * 1993-01-08 1995-05-30 Pdt Systems, Inc. Medicament dispensing stent for prevention of restenosis of a blood vessel
US6491938B2 (en) * 1993-05-13 2002-12-10 Neorx Corporation Therapeutic inhibitor of vascular smooth muscle cells
US6663881B2 (en) 1993-01-28 2003-12-16 Neorx Corporation Therapeutic inhibitor of vascular smooth muscle cells
US5981568A (en) * 1993-01-28 1999-11-09 Neorx Corporation Therapeutic inhibitor of vascular smooth muscle cells
US5439686A (en) 1993-02-22 1995-08-08 Vivorx Pharmaceuticals, Inc. Methods for in vivo delivery of substantially water insoluble pharmacologically active agents and compositions useful therefor
US5378456A (en) * 1993-03-25 1995-01-03 American Cyanamid Company Antitumor mitoxantrone polymeric compositions
WO1994024961A1 (en) 1993-04-23 1994-11-10 Schneider (Usa) Inc. Covered stent and stent delivery device
US5464650A (en) 1993-04-26 1995-11-07 Medtronic, Inc. Intravascular stent and method
WO1994026291A1 (en) * 1993-05-13 1994-11-24 Neorx Corporation Therapeutic inhibitor of vascular smooth muscle cells
IT1276342B1 (it) 1993-06-04 1997-10-30 Ist Naz Stud Cura Dei Tumori Stent metallico rivestito con materiale polimerico biocompatibile
US5468769A (en) 1993-07-15 1995-11-21 Abbott Laboratories Paclitaxel derivatives
US5716981A (en) 1993-07-19 1998-02-10 Angiogenesis Technologies, Inc. Anti-angiogenic compositions and methods of use
AU771815B2 (en) 1993-07-19 2004-04-01 Angiotech Pharmaceuticals, Inc. Anti-angiogenic compositions and methods of use
CN100998565A (zh) * 1993-07-19 2007-07-18 血管技术药物公司 抗血管生长组合物及使用方法
US20030203976A1 (en) * 1993-07-19 2003-10-30 William L. Hunter Anti-angiogenic compositions and methods of use
AU728873B2 (en) 1993-07-19 2001-01-18 Angiotech Pharmaceuticals, Inc. Anti-angiogenic compositions and methods of use
DE69434598T3 (de) 1993-07-29 2010-07-29 The United States Of America Represented By The Secretary, Department Of Health And Human Services Verwendung von Paclitaxel und seinen Derivaten zur Herstellung eines Medikaments für die Behandlung von Restenose
US5380299A (en) * 1993-08-30 1995-01-10 Med Institute, Inc. Thrombolytic treated intravascular medical device
US5455046A (en) 1993-09-09 1995-10-03 Edward Mendell Co., Inc. Sustained release heterodisperse hydrogel systems for insoluble drugs
US5457113A (en) * 1993-10-15 1995-10-10 Eli Lilly And Company Methods for inhibiting vascular smooth muscle cell proliferation and restinosis
US5643575A (en) 1993-10-27 1997-07-01 Enzon, Inc. Non-antigenic branched polymer conjugates
US5415869A (en) 1993-11-12 1995-05-16 The Research Foundation Of State University Of New York Taxol formulation
US5443505A (en) 1993-11-15 1995-08-22 Oculex Pharmaceuticals, Inc. Biocompatible ocular implants
WO1995013830A1 (en) * 1993-11-17 1995-05-26 Massachusetts Institute Of Technology Method for inhibiting angiogenesis using heparinase
US5462726A (en) 1993-12-17 1995-10-31 Bristol-Myers Squibb Company Method of inhibiting side effects of solvents containing ricinoleic acid or castor oil or derivatives thereof employing a thromboxane A2 receptor antagonist and pharmaceutical compositions containing such solvents
CA2147813A1 (en) 1994-04-28 1995-10-29 Richard Dixon Intravascular prosthesis with anti-thrombogenic coating
US5626862A (en) * 1994-08-02 1997-05-06 Massachusetts Institute Of Technology Controlled local delivery of chemotherapeutic agents for treating solid tumors
US5489589A (en) 1994-12-07 1996-02-06 Bristol-Myers Squibb Company Amino acid derivatives of paclitaxel
US6231600B1 (en) 1995-02-22 2001-05-15 Scimed Life Systems, Inc. Stents with hybrid coating for medical devices
JP3224121B2 (ja) 1995-04-24 2001-10-29 ヤマハ発動機株式会社 自動二輪車用ステアリングヘッド部材
US5801191A (en) 1995-06-01 1998-09-01 Biophysica Foundation Taxoids
US5766584A (en) 1995-06-02 1998-06-16 Massachusetts Institute Of Technology Inhibition of vascular smooth muscle cell proliferation with implanted matrix containing vascular endothelial cells
US6783543B2 (en) * 2000-06-05 2004-08-31 Scimed Life Systems, Inc. Intravascular stent with increasing coating retaining capacity
DE69734060T2 (de) * 1996-05-24 2006-06-29 Angiotech Pharmaceuticals, Inc., Vancouver Zubereitungen und verfahren zur behandlung oder prävention von krankheiten der körperpassagewege
CA2288198A1 (en) 1997-03-25 1998-10-01 Daniel I. Simon Modulation of vascular healing by inhibition of leukocyte adhesion and function
ES2226120T3 (es) 1997-03-31 2005-03-16 Boston Scientific Limited Inhibidor terapeutico de celulas del musculo liso vascular.
US6273908B1 (en) * 1997-10-24 2001-08-14 Robert Ndondo-Lay Stents
EP1042003A1 (en) 1998-03-23 2000-10-11 Conjuchem, Inc. Delivery of long lasting therapeutic agents by forming covalent attachments in vivo
US6241762B1 (en) * 1998-03-30 2001-06-05 Conor Medsystems, Inc. Expandable medical device with ductile hinges
US7208010B2 (en) 2000-10-16 2007-04-24 Conor Medsystems, Inc. Expandable medical device for delivery of beneficial agent
EP1132058A1 (en) 2000-03-06 2001-09-12 Advanced Laser Applications Holding S.A. Intravascular prothesis
US6395326B1 (en) * 2000-05-31 2002-05-28 Advanced Cardiovascular Systems, Inc. Apparatus and method for depositing a coating onto a surface of a prosthesis
AU2002235175A1 (en) 2000-12-06 2002-06-18 Tularik, Inc. Lometrexol combination therapy
JP3502053B2 (ja) 2001-03-15 2004-03-02 パナソニック コミュニケーションズ株式会社 複合機
CN100436678C (zh) * 2002-06-20 2008-11-26 费德罗-莫格尔动力系公司 多层隔离套筒
JP3990961B2 (ja) * 2002-09-09 2007-10-17 株式会社コナミデジタルエンタテインメント ゲーム機およびビンゴゲーム機
US20040127976A1 (en) * 2002-09-20 2004-07-01 Conor Medsystems, Inc. Method and apparatus for loading a beneficial agent into an expandable medical device
US20070003636A1 (en) * 2003-01-22 2007-01-04 Francois Mach Statins (HMG-COA reductase inhibitors) as a novel type of immunomodulator, immunosuppressor and anti-inflammatory agent
US20050100577A1 (en) 2003-11-10 2005-05-12 Parker Theodore L. Expandable medical device with beneficial agent matrix formed by a multi solvent system

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0375520A1 (fr) * 1988-12-20 1990-06-27 Centre International De Recherches Dermatologiques Galderma - Cird Galderma Composition cosmétique ou pharmaceutique contenant des microsphères de polymères ou de corps gras chargées d'au moins un produit actif
WO1991010424A1 (en) * 1990-01-12 1991-07-25 Northwestern University Method of inhibiting angiogenesis of tumors
WO1991011193A1 (en) * 1990-01-25 1991-08-08 Children's Hospital Method and compositions for inhibiting angiogenesis
EP0470569A1 (en) * 1990-08-08 1992-02-12 Takeda Chemical Industries, Ltd. Intravascular embolizing agent containing angiogenesis inhibiting substance
WO1992012717A2 (en) * 1991-01-15 1992-08-06 A composition containing a tetracycline and use for inhibiting angiogenesis
WO1992015286A1 (en) * 1991-02-27 1992-09-17 Nova Pharmaceutical Corporation Anti-infective and anti-inflammatory releasing systems for medical devices
EP0567816A1 (de) * 1992-04-30 1993-11-03 BEHRINGWERKE Aktiengesellschaft Verwendung von Inhibitoren von Plasminogenaktivatoren zur Behandlung von Entzündungen und Wunden

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
K.A. WALTER ET AL.: "interstitial taxol delivered from a biodegradable polymer implant against experimental malignant glioma", CANCER RESEARCH, vol. 54, 15 April 1994 (1994-04-15), BALTIMORE, MD(US), pages 2207 - 2212 *
M.-H. BARTOLI: "in vitro and in vivo antitumoral activity of free and encapsulated taxol", JOURNAL OF MICROENCAPSULATION, vol. 7, no. 2, May 1990 (1990-05-01), LONDON (GB), pages 191 - 197 *

Cited By (221)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7820193B2 (en) 1993-07-19 2010-10-26 Angiotech Pharmaceuticals, Inc. Anti-angiogenic compositions and methods of use
US5716981A (en) * 1993-07-19 1998-02-10 Angiogenesis Technologies, Inc. Anti-angiogenic compositions and methods of use
US5994341A (en) * 1993-07-19 1999-11-30 Angiogenesis Technologies, Inc. Anti-angiogenic Compositions and methods for the treatment of arthritis
US6846841B2 (en) 1993-07-19 2005-01-25 Angiotech Pharmaceuticals, Inc. Anti-angiogenic compositions and methods of use
EP1118325A2 (en) † 1993-07-29 2001-07-25 The United States of America, represented by the Secretary, Department of Health and Human Services Drug delivery systems containing microtubule stabilizing agents and the use of said agents in the manufacture of a medicament for treating atherosclerosis or restenosis
EP1118325B2 (en) † 1993-07-29 2010-01-06 The United States of America, represented by the Secretary, Department of Health and Human Services Use of Paclitaxel and its derivatives in the manufacture of a medicament for treating restenosis.
US6403635B1 (en) 1993-07-29 2002-06-11 The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Method of treating atherosclerosis or restenosis using microtubule stabilizing agent
US6429232B1 (en) 1993-07-29 2002-08-06 The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Method of treating atherosclerosis or restenosis using microtubule stabilizing agent
US6500859B2 (en) 1993-07-29 2002-12-31 The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Method for treating atherosclerosis or restenosis using microtubule stabilizing agent
US5616608A (en) * 1993-07-29 1997-04-01 The United States Of America As Represented By The Department Of Health And Human Services Method of treating atherosclerosis or restenosis using microtubule stabilizing agent
US6025334A (en) * 1994-04-28 2000-02-15 Les Laboratoires Aeterna Inc. Extracts of shark cartilage having anti-collagenolytic, anti-inflammatory, anti-angiogenic and anti-tumoral activities; process of making, methods of using and compositions thereof
US5985839A (en) * 1994-04-28 1999-11-16 Les Laboratories Aeterna Inc. Extracts of shark cartilage having an anti-angiogenic activity and an effect on tumor regression: process of making thereof
US5618925A (en) * 1994-04-28 1997-04-08 Les Laboratories Aeterna Inc. Extracts of shark cartilage having an anti-angiogenic activity and an effect on tumor regression; process of making thereof
US6380366B1 (en) 1994-04-28 2002-04-30 Les Laboratoires Aeterna Inc. Shark cartilage extract:process of making, methods of using and compositions thereof
WO1995032722A1 (en) * 1994-04-28 1995-12-07 Les Laboratoires Aeterna Inc. Extracts of shark cartilage having an anti-angiogenic activity and an effect on tumor regression; process of making thereof
US6635285B2 (en) 1994-04-28 2003-10-21 Les Laboratoires Aeterna, Inc. Shark cartilage extract: process of making, methods of using, and compositions thereof
EP1407786A1 (en) * 1995-02-15 2004-04-14 SciMed Life Systems, Inc. Therapeutic inhibitor of vascular smooth muscle cells
EP1669091A3 (en) * 1995-02-15 2009-06-17 Boston Scientific Limited Therapeutic inhibitor of vascular smooth muscle cells
US6171609B1 (en) 1995-02-15 2001-01-09 Neorx Corporation Therapeutic inhibitor of vascular smooth muscle cells
JP2007075623A (ja) * 1995-02-15 2007-03-29 Boston Scientific Ltd 血管平滑筋細胞の治療インヒビター
WO1996025176A1 (en) * 1995-02-15 1996-08-22 Neorx Corporation Therapeutic inhibitor of vascular smooth muscle cells
EP0734721A2 (en) * 1995-03-30 1996-10-02 Advanced Cardiovascular Systems, Inc. Method of incorporating drugs into a polymer component of stents
US6774278B1 (en) 1995-06-07 2004-08-10 Cook Incorporated Coated implantable medical device
US7862605B2 (en) 1995-06-07 2011-01-04 Med Institute, Inc. Coated implantable medical device
US7060724B2 (en) 1996-03-12 2006-06-13 Pg-Txl Company, L.P. Water soluble paclitaxel derivatives
US6884817B2 (en) 1996-03-12 2005-04-26 Pg-Txl Company, L.P. Water soluble paclitaxel derivatives
US7135496B2 (en) 1996-03-12 2006-11-14 Pg-Txl Company, L.P. Water soluble paclitaxel derivatives
US7384977B2 (en) 1996-03-12 2008-06-10 Pg-Txl Company, L.P. Water soluble paclitaxel prodrugs
US6441025B2 (en) 1996-03-12 2002-08-27 Pg-Txl Company, L.P. Water soluble paclitaxel derivatives
US5977163A (en) * 1996-03-12 1999-11-02 Pg-Txl Company, L. P. Water soluble paclitaxel prodrugs
AU775787B2 (en) * 1996-05-24 2004-08-12 Angiotech Pharmaceuticals, Inc. Compositions and methods for treating or preventing diseases of body passageways
WO1997045105A1 (en) * 1996-05-24 1997-12-04 Angiotech Pharmaceuticals, Inc. Compositions and methods for treating or preventing diseases of body passageways
EP1616563A3 (en) * 1996-05-24 2006-01-25 Angiotech Pharmaceuticals, Inc. Perivascular administration of anti-angiogenic factors for treating or preventing vascular diseases
JP2004285074A (ja) * 1996-05-24 2004-10-14 Angiotech Pharmaceuticals Inc 身体通路の疾患を処置または予防するための組成物および方法
EP1616563A2 (en) * 1996-05-24 2006-01-18 Angiotech Pharmaceuticals, Inc. Perivascular administration of anti-angiogenic factors for treating or preventing vascular diseases
EP0910301A1 (en) * 1996-06-12 1999-04-28 The Regents Of The University Of Michigan Compositions and methods for coating medical devices
EP0910301A4 (en) * 1996-06-12 2004-10-27 Univ Michigan COMPOSITIONS AND METHODS FOR CLOTHING MEDICAL DEVICES
JP2009102418A (ja) * 1996-06-12 2009-05-14 Regents Of The Univ Of Michigan 医療用具をコーティングするための組成物及び方法
WO1998000183A2 (en) * 1996-06-28 1998-01-08 Shaw, Robert, Francis Methods and compositions for the treatment and repair of defects or lesions in cartilage or bone using functional barrier
CN1321681C (zh) * 1996-06-28 2007-06-20 罗伯特·弗朗西斯·肖 使用功能性屏障治疗和修复软骨或骨缺损或损伤的方法及组合物
WO1998000183A3 (en) * 1996-06-28 1998-02-12 Shaw Robert F Methods and compositions for the treatment and repair of defects or lesions in cartilage or bone using functional barrier
AU731172B2 (en) * 1996-06-28 2001-03-22 Shaw, Robert Francis Methods and compositions for the treatment and repair of defects or lesions in cartilage or bone using functional barrier
US6028118A (en) * 1996-08-08 2000-02-22 Les Laboratoires Aeterna Inc. Methods of using extracts of shark cartilage
US6515016B2 (en) 1996-12-02 2003-02-04 Angiotech Pharmaceuticals, Inc. Composition and methods of paclitaxel for treating psoriasis
US6495579B1 (en) 1996-12-02 2002-12-17 Angiotech Pharmaceuticals, Inc. Method for treating multiple sclerosis
US6383522B1 (en) 1997-03-11 2002-05-07 Les Laboratoires Aeterna, Inc. Toxicity reduced composition containing an anti-neoplastic agent and a shark cartilage extract
US6855338B2 (en) 1997-03-11 2005-02-15 Les Laboratoires Aeterna, Inc. Anti-tumor therapies comprising a combination of a cartilage extract and an anti-neoplastic agent providing high efficacy and low toxic side effects
US7998105B2 (en) 1997-03-13 2011-08-16 Biocardia, Inc. Method of treating coronary arteries with perivascular delivery of therapeutic agents
EP2098230A1 (en) 1997-03-31 2009-09-09 Boston Scientific Scimed Limited Use of cytoskeletal inhibitors in crystalline form for the inhibition or prevention of restenosis
US8853260B2 (en) 1997-06-27 2014-10-07 Abraxis Bioscience, Llc Formulations of pharmacological agents, methods for the preparation thereof and methods for the use thereof
WO1999008729A1 (en) * 1997-08-13 1999-02-25 Boston Scientific Limited Loading and release of water-insoluble drugs
US6306166B1 (en) 1997-08-13 2001-10-23 Scimed Life Systems, Inc. Loading and release of water-insoluble drugs
EP1010435B1 (en) * 1997-09-05 2010-11-03 Maruho K.K. Nanocapsule preparations for treating intraarticular diseases
EP1010435A1 (en) * 1997-09-05 2000-06-21 Maruho K.K. Nanocapsule preparations for treating intraarticular diseases
DE19744135C1 (de) * 1997-09-29 1999-03-25 Schering Ag Beschichtete medizinische Implantate, Verfahren zu ihrer Herstellung und ihre Verwendung zur Restenoseprophylaxe
US6485514B1 (en) 1997-12-12 2002-11-26 Supergen, Inc. Local delivery of therapeutic agents
US6589547B1 (en) 1998-03-04 2003-07-08 Takeda Chemical Industries, Ltd. Sustained-release preparation for AII antagonist, production and use thereof
WO1999044590A1 (en) * 1998-03-04 1999-09-10 Takeda Chemical Industries, Ltd. Sustained-release preparation for aii antagonist, production and use thereof
US8052735B2 (en) 1998-03-30 2011-11-08 Innovational Holdings, Llc Expandable medical device with ductile hinges
US8623068B2 (en) 1998-03-30 2014-01-07 Conor Medsystems, Inc. Expandable medical device with ductile hinges
US7819912B2 (en) 1998-03-30 2010-10-26 Innovational Holdings Llc Expandable medical device with beneficial agent delivery mechanism
US8439968B2 (en) 1998-03-30 2013-05-14 Innovational Holdings, Llc Expandable medical device for delivery of beneficial agent
US7896912B2 (en) 1998-03-30 2011-03-01 Innovational Holdings, Llc Expandable medical device with S-shaped bridging elements
US8361537B2 (en) 1998-03-30 2013-01-29 Innovational Holdings, Llc Expandable medical device with beneficial agent concentration gradient
US8206435B2 (en) 1998-03-30 2012-06-26 Conor Medsystems, Inc. Expandable medical device for delivery of beneficial agent
US8052734B2 (en) 1998-03-30 2011-11-08 Innovational Holdings, Llc Expandable medical device with beneficial agent delivery mechanism
US6168807B1 (en) 1998-07-23 2001-01-02 Les Laboratoires Aeterna Inc. Low molecular weight components of shark cartilage, processes for their preparation and therapeutic uses thereof
US6506414B2 (en) 1998-07-23 2003-01-14 Les Laboratoires Aeterna Inc. Low molecular weight components of shark cartilage, processes for their preparation and therapeutic uses thereof
US6730064B2 (en) 1998-08-20 2004-05-04 Cook Incorporated Coated implantable medical device
WO2000010552A3 (en) * 1998-08-24 2000-11-23 Global Vascular Concepts Inc Use of anti-angiogenic agents for inhibiting vessel wall injury
WO2000010552A2 (en) * 1998-08-24 2000-03-02 Global Vascular Concepts, Inc. Use of anti-angiogenic agents for inhibiting vessel wall injury
WO2000021584A1 (en) * 1998-10-14 2000-04-20 Boston Scientific Limited Loading and release of water-insoluble drugs
EP1800702A3 (en) * 1998-10-14 2008-03-05 Boston Scientific Limited Loading and release of water-insoluble drugs
WO2000032238A1 (en) * 1998-12-03 2000-06-08 Scimed Life Systems, Inc. Stent having drug crystals thereon
WO2000050016A3 (en) * 1999-02-23 2001-01-18 Angiotech Pharm Inc Compositions and methods for improving integrity of compromised body passageways and cavities
WO2000050016A2 (en) * 1999-02-23 2000-08-31 Angiotech Pharmaceuticals, Inc. Compositions and methods for improving integrity of compromised body passageways and cavities
WO2000056283A1 (en) * 1999-03-24 2000-09-28 The B.F.Goodrich Company Inhibition of matrix metalloproteinases with polymers and pharmaceutical applications thereof
WO2001036007A2 (en) * 1999-11-12 2001-05-25 Angiotech Pharmaceuticals, Inc. Compositions of a combination of radioactive therapy and cell-cycle inhibitors
WO2001036007A3 (en) * 1999-11-12 2002-07-04 Angiotech Pharm Inc Compositions of a combination of radioactive therapy and cell-cycle inhibitors
EP1278493A1 (en) * 1999-12-29 2003-01-29 Estrogen Vascular Technology, LLC Apparatus and method for delivering compounds to a living organism
EP1278493A4 (en) * 1999-12-29 2006-09-27 Cell Medical Inc X DEVICE AND METHOD FOR ADMINISTERING COMPOUNDS TO LIVING ORGANISM
US8883856B2 (en) * 2000-02-28 2014-11-11 John Jackson Compositions and methods for the treatment of inflammatory diseases using topoisomerase inhibitors
US7173041B2 (en) 2000-03-17 2007-02-06 Cell Therapeutics Inc. Polyglutamic acid-camptothecin conjugates and methods of preparation
US7153864B2 (en) 2000-03-17 2006-12-26 Cell Therapeutics Inc. Polyglutamic acid-camptothecin conjugates and methods of preparation
US8096972B2 (en) 2000-08-30 2012-01-17 Johns Hopkins University Devices for intraocular drug delivery
EP1322235B2 (en) † 2000-09-29 2010-08-11 Cordis Corporation Coated medical devices
US7850728B2 (en) 2000-10-16 2010-12-14 Innovational Holdings Llc Expandable medical device for delivery of beneficial agent
US8187321B2 (en) 2000-10-16 2012-05-29 Innovational Holdings, Llc Expandable medical device for delivery of beneficial agent
US6746661B2 (en) 2000-11-16 2004-06-08 Microspherix Llc Brachytherapy seed
US10994058B2 (en) 2000-11-16 2021-05-04 Microspherix Llc Method for administering a flexible hormone rod
US10493181B2 (en) 2000-11-16 2019-12-03 Microspherix Llc Flexible and/or elastic brachytherapy seed or strand
US7425217B2 (en) 2000-11-16 2008-09-16 Maier Nathan C System and method for inhibiting cellular proliferation with tachykinins
WO2002068000A3 (en) * 2000-11-16 2003-10-23 Microspherix Llc Polymeric imagable brachytherapy seed
WO2002068000A2 (en) * 2000-11-16 2002-09-06 Microspherix Llc Polymeric imagable brachytherapy seed
US9636402B2 (en) 2000-11-16 2017-05-02 Microspherix Llc Flexible and/or elastic brachytherapy seed or strand
US7776310B2 (en) 2000-11-16 2010-08-17 Microspherix Llc Flexible and/or elastic brachytherapy seed or strand
US9636401B2 (en) 2000-11-16 2017-05-02 Microspherix Llc Flexible and/or elastic brachytherapy seed or strand
US8057814B2 (en) 2001-01-11 2011-11-15 Abbott Laboratories Drug delivery from stents
US8512750B2 (en) 2001-01-11 2013-08-20 Abbott Laboratories Stents with drug-containing amphiphilic polymer coating
WO2002055121A1 (en) * 2001-01-11 2002-07-18 Biocompatibles Uk Limited Drug delivery from stents
US8512733B2 (en) 2001-01-11 2013-08-20 Abbott Laboratories Stents with drug-containing amphiphilic polymer coating
US8465758B2 (en) 2001-01-11 2013-06-18 Abbott Laboratories Drug delivery from stents
US7713538B2 (en) 2001-01-11 2010-05-11 Abbott Laboratories Drug delivery from stents
US8097236B2 (en) 2001-02-22 2012-01-17 Psimedica Limited Devices and methods for the treatment of cancer
US7771468B2 (en) 2001-03-16 2010-08-10 Angiotech Biocoatings Corp. Medicated stent having multi-layer polymer coating
US8287590B2 (en) 2001-03-16 2012-10-16 Angiotech Biocoatings Corp. Medicated stent having multi-layer polymer coating
US9066990B2 (en) 2001-03-26 2015-06-30 Bayer Intellectual Property Gmbh Preparation for restenosis prevention
US7750041B2 (en) 2001-03-26 2010-07-06 Bayer Schering Pharma Aktiengesellschaft Preparation for the prophylaxis of restenosis
US7875677B2 (en) 2001-04-20 2011-01-25 The University Of British Columbia Micellar drug delivery systems for hydrophobic drugs
US7651695B2 (en) 2001-05-18 2010-01-26 Advanced Cardiovascular Systems, Inc. Medicated stents for the treatment of vascular disease
WO2002094335A1 (en) * 2001-05-18 2002-11-28 Advanced Cardiovascular Systems, Inc. Medicated stents for the treatment of vascular disease
WO2003089005A1 (fr) * 2002-04-22 2003-10-30 Reserach Foundation Itsuu Laboratory Medicaments de traitement de maladies vasculaires
KR100995225B1 (ko) 2002-04-22 2010-11-17 재단법인 이쯔우 연구소 혈관성 질환의 치료를 위한 의약
AU2003227454B2 (en) * 2002-04-22 2009-07-30 Research Foundation Itsuu Laboratory Medicament for therapeutic treatment of vascular disease
US8372420B2 (en) 2002-05-24 2013-02-12 Angiotech International Ag Compositions and methods for coating medical implants
US8313760B2 (en) 2002-05-24 2012-11-20 Angiotech International Ag Compositions and methods for coating medical implants
US9265836B2 (en) 2002-06-11 2016-02-23 Protherics Salt Lake City, Inc. Biodegradable block copolymeric compositions for drug delivery
US10398724B2 (en) 2002-06-12 2019-09-03 Boston Scientific Scimed, Inc. Bulking agents
US8439868B2 (en) 2002-09-20 2013-05-14 Bayer Pharma AG Medical device for dispersing medicaments
US8349390B2 (en) 2002-09-20 2013-01-08 Conor Medsystems, Inc. Method and apparatus for loading a beneficial agent into an expandable medical device
US9254202B2 (en) 2002-09-20 2016-02-09 Innovational Holdings Llc Method and apparatus for loading a beneficial agent into an expandable medical device
US8257305B2 (en) 2002-09-20 2012-09-04 Bayer Pharma Aktiengesellschaft Medical device for dispensing medicaments
US9649476B2 (en) 2002-09-20 2017-05-16 Bayer Intellectual Property Gmbh Medical device for dispersing medicaments
US9012518B2 (en) 2002-12-09 2015-04-21 Abraxis Bioscience, Llc Compositions and methods of delivery of pharmacological agents
US9012519B2 (en) 2002-12-09 2015-04-21 Abraxis Bioscience, Llc Compositions and methods of delivery of pharmacological agents
US8846771B2 (en) 2002-12-09 2014-09-30 Abraxis Bioscience, Llc Compositions and methods of delivery of pharmacological agents
US7820788B2 (en) 2002-12-09 2010-10-26 Abraxis Bioscience, Llc Compositions and methods of delivery of pharmacological agents
WO2005027951A1 (en) * 2003-09-16 2005-03-31 Glycogenesys, Inc. Method for controlling angiogenesis in animals
US8197881B2 (en) 2003-09-22 2012-06-12 Conor Medsystems, Inc. Method and apparatus for loading a beneficial agent into an expandable medical device
US8940311B2 (en) 2004-10-21 2015-01-27 Tae-Hong Lim In situ controlled release drug delivery system
EP1807018A4 (en) * 2004-10-21 2012-07-04 Univ Iowa Res Found SYSTEM FOR CONTROLLED IN-SITU ADMINISTRATION OF MEDICINAL PRODUCTS
EP1807018A2 (en) * 2004-10-21 2007-07-18 University of Iowa Research Foundation In situ controlled release drug delivery system
EA012083B1 (ru) * 2005-02-03 2009-08-28 Синвеншен Аг Материал для доставки лекарств, способ его получения и имплантат, содержащий этот материал
WO2006082221A1 (en) * 2005-02-03 2006-08-10 Cinvention Ag Drug delivery materials made by sol/gel technology
US9050393B2 (en) 2005-02-08 2015-06-09 Bruce N. Saffran Medical devices and methods for modulation of physiology using device-based surface chemistry
US8268348B2 (en) 2005-02-18 2012-09-18 Abraxis Bioscience, Llc Combinations and modes of administration of therapeutic agents and combination therapy
US7758891B2 (en) 2005-02-18 2010-07-20 Abraxis Bioscience, Llc Combinations and modes of administration of therapeutic agents and combination therapy
US9101543B2 (en) 2005-02-18 2015-08-11 Abraxis Bioscience, Llc Combinations and modes of administration of therapeutic agents and combination therapy
EP3248600B1 (en) 2005-02-18 2020-04-08 Abraxis BioScience, LLC Combinations and modes of administration of therapeutic agents and combination therapy
US9561288B2 (en) 2005-02-18 2017-02-07 Abraxis Bioscience, Llc Combinations and modes of administration of therapeutic agents and combination therapy
US8735394B2 (en) 2005-02-18 2014-05-27 Abraxis Bioscience, Llc Combinations and modes of administration of therapeutic agents and combination therapy
US8574604B2 (en) 2005-04-15 2013-11-05 Interface Biologics, Inc. Methods and compositions for the delivery of biologically active agents
US9283035B2 (en) 2005-04-28 2016-03-15 Boston Scientific Scimed, Inc. Tissue-treatment methods
US7560112B2 (en) 2005-04-29 2009-07-14 Applied Molecular Evolution, Inc. Anti-il-6 antibodies, compositions, methods and uses
US8067003B2 (en) 2005-04-29 2011-11-29 Centocor, Inc. Methods of treating conditions using anti-IL-6 antibodies
US7833755B2 (en) 2005-04-29 2010-11-16 Yan Chen Anti-IL-6 antibody nucleic acid molecules and methods
US11180549B2 (en) 2005-04-29 2021-11-23 Janssen Biotech, Inc. Methods of suppressing rheumatoid arthritis using an anti-IL-6 antibody
US9340613B2 (en) 2005-04-29 2016-05-17 Janssen Biotech, Inc. Anti-IL-6 antibodies, compositions, methods and uses
US8623362B2 (en) 2005-04-29 2014-01-07 Janssen Biotech, Inc. Anti-IL-6 antibodies
US9631016B2 (en) 2005-04-29 2017-04-25 Janssen Biotech, Inc. Pen-injector device containing anti-IL-6 antibodies
US8226611B2 (en) 2005-04-29 2012-07-24 Janssen Biotech, Inc. Anti-IL-6 antibodies, compositions, methods and uses
USRE43672E1 (en) 2005-04-29 2012-09-18 Janssen Biotech, Inc. Anti-IL-6 antibodies, compositions, methods and uses
US9463426B2 (en) 2005-06-24 2016-10-11 Boston Scientific Scimed, Inc. Methods and systems for coating particles
US8192483B2 (en) 2005-10-06 2012-06-05 Kaneka Corporation Stent to be placed in the living body
CN100464736C (zh) * 2006-03-17 2009-03-04 山东蓝金生物工程有限公司 同载抗代谢药物及其增效剂的抗癌缓释注射剂
US8691288B2 (en) 2006-05-10 2014-04-08 Medtronic, Inc. Gallium-containing sealant for medical use
US8632809B2 (en) 2006-11-09 2014-01-21 Alcon Research, Ltd. Water insoluble polymer matrix for drug delivery
US9119896B2 (en) 2007-02-08 2015-09-01 Medtronic Xomed, Inc. Polymeric sealant for medical use
US9192697B2 (en) 2007-07-03 2015-11-24 Hemoteq Ag Balloon catheter for treating stenosis of body passages and for preventing threatening restenosis
DE102008008263A1 (de) 2008-02-08 2009-08-13 Thomas Kuczera Restenoseprophylaxe
US10426779B2 (en) 2008-04-10 2019-10-01 Virginia Commonwealth University Induction of tumor hypoxia for cancer therapy
US8591921B2 (en) 2008-04-10 2013-11-26 Virginia Commonwealth University Induction of tumor hypoxia for cancer therapy
US10159676B2 (en) 2008-04-10 2018-12-25 Virginia Commonwealth University Induction of tumor hypoxia for cancer therapy
US9649316B2 (en) 2008-04-10 2017-05-16 Virginia Commonwealth University Induction of tumor hypoxia for cancer therapy
DE202008006190U1 (de) 2008-05-06 2008-07-17 Sellin, Lothar Restenoseprophylaxe
DE102008063889A1 (de) 2008-05-06 2009-11-26 Lothar Sellin Medizinische Einrichtung und Verfahren zu ihrer Herstellung
DE202008007347U1 (de) 2008-05-31 2008-10-16 Orlowski, Benjamin Daniel Kupfer Stent
US9700344B2 (en) 2008-06-12 2017-07-11 Medtronic Xomed, Inc. Method for treating chronic wounds with an extracellular polymeric substance solvating system
US8846037B2 (en) 2008-06-18 2014-09-30 Pfizer Inc. Antibodies to IL-6 and their uses
US8188235B2 (en) 2008-06-18 2012-05-29 Pfizer Inc. Antibodies to IL-6 and their uses
US8436158B2 (en) 2008-06-18 2013-05-07 Pfizer Inc. Antibodies to IL-6 and their uses
US10463619B2 (en) 2008-06-27 2019-11-05 Tepha, Inc. Injectable delivery of microparticles and compositions therefor
WO2009158724A3 (en) * 2008-06-27 2011-03-31 Tepha, Inc. Injectable delivery of microparticles and compos itions therefore
US9216152B2 (en) 2008-06-27 2015-12-22 Tepha, Inc. Injectable delivery of microparticles and compositions therefore
US9132211B2 (en) 2008-09-15 2015-09-15 The Spectranetics Corporation Local delivery of water-soluble or water-insoluble therapeutic agents to the surface of body lumens
US10046093B2 (en) 2008-09-15 2018-08-14 The Spectranetics Corporation Local delivery of water-soluble or water-insoluble therapeutic agents to the surface of body lumens
US9034362B2 (en) 2008-09-15 2015-05-19 The Spectranetics Corporation Local delivery of water-soluble or water-insoluble therapeutic agents to the surface of body lumens
US9603973B2 (en) 2008-09-15 2017-03-28 The Spectranetics Corporation Local delivery of water-soluble or water-insoluble therapeutic agents to the surface of body lumens
US10987452B2 (en) 2008-09-15 2021-04-27 The Spectranetics Corporation Local delivery of water-soluble or water-insoluble therapeutic agents to the surface of body lumens
US8734825B2 (en) 2008-09-15 2014-05-27 Covidien Lp Local delivery of water-soluble or water-insoluble therapeutic agents to the surface of body lumens
US10314948B2 (en) 2008-09-15 2019-06-11 The Spectranetics Coporation Local delivery of water-soluble or water-insoluble therapeutic agents to the surface of body lumens
US9198968B2 (en) 2008-09-15 2015-12-01 The Spectranetics Corporation Local delivery of water-soluble or water-insoluble therapeutic agents to the surface of body lumens
US10117970B2 (en) 2008-09-15 2018-11-06 The Spectranetics Corporation Local delivery of water-soluble or water-insoluble therapeutic agents to the surface of body lumens
DE102009059070A1 (de) 2008-12-19 2010-07-01 Lothar Sellin Medizinische Einrichtung und Verfahren zu ihrer Herstellung
US11278648B2 (en) 2009-07-10 2022-03-22 Boston Scientific Scimed, Inc. Use of nanocrystals for drug delivery from a balloon
US10369256B2 (en) 2009-07-10 2019-08-06 Boston Scientific Scimed, Inc. Use of nanocrystals for drug delivery from a balloon
US10080821B2 (en) 2009-07-17 2018-09-25 Boston Scientific Scimed, Inc. Nucleation of drug delivery balloons to provide improved crystal size and density
US9597409B2 (en) 2010-03-29 2017-03-21 Abraxis Bioscience, Llc Methods of treating cancer
US9393318B2 (en) 2010-03-29 2016-07-19 Abraxis Bioscience, Llc Methods of treating cancer
US10660965B2 (en) 2010-03-29 2020-05-26 Abraxis Bioscience, Llc Methods of enhancing drug delivery and effectiveness of therapeutic agents
US9820949B2 (en) 2010-06-04 2017-11-21 Abraxis Bioscience, Llc Methods of treatment of pancreatic cancer
US9399072B2 (en) 2010-06-04 2016-07-26 Abraxis Bioscience, Llc Methods of treatment of pancreatic cancer
US9399071B2 (en) 2010-06-04 2016-07-26 Abraxis Bioscience, Llc Methods of treatment of pancreatic cancer
US8889211B2 (en) 2010-09-02 2014-11-18 Boston Scientific Scimed, Inc. Coating process for drug delivery balloons using heat-induced rewrap memory
US8884027B2 (en) 2010-10-22 2014-11-11 University Of Rochester Melampomagnolide B derivatives as antileukemic and cytotoxic agents
US9056152B2 (en) 2011-08-25 2015-06-16 Boston Scientific Scimed, Inc. Medical device with crystalline drug coating
US9308355B2 (en) 2012-06-01 2016-04-12 Surmodies, Inc. Apparatus and methods for coating medical devices
US10099041B2 (en) 2012-06-01 2018-10-16 Surmodics, Inc. Apparatus and methods for coating medical devices
US9827401B2 (en) 2012-06-01 2017-11-28 Surmodics, Inc. Apparatus and methods for coating medical devices
US10507309B2 (en) 2012-06-01 2019-12-17 Surmodics, Inc. Apparatus and methods for coating medical devices
US9623215B2 (en) 2012-06-01 2017-04-18 Surmodics, Inc. Apparatus and methods for coating medical devices
US9956385B2 (en) 2012-06-28 2018-05-01 The Spectranetics Corporation Post-processing of a medical device to control morphology and mechanical properties
US10842969B2 (en) 2013-10-25 2020-11-24 Mercator Medsystems, Inc. Systems and methods of treating malacia by local delivery of hydrogel to augment tissue
US10525171B2 (en) 2014-01-24 2020-01-07 The Spectranetics Corporation Coatings for medical devices
DE202015002048U1 (de) 2015-03-16 2015-09-24 Han Bock-Sun Implantat
DE102016003023A1 (de) 2015-03-16 2016-09-22 Bock-Sun Han Implantat
RU2693042C2 (ru) * 2015-04-20 2019-07-01 Тгель Био Ко., Лтд. Набор для доставки лекарственного средства, и устройство, и способ, предназначенные для получения системы для доставки лекарственного средства
US10391233B2 (en) 2015-04-20 2019-08-27 Tgel Bio Co., Ltd. Drug delivery kit, and apparatus and method for preparing drug delivery system
US11331278B2 (en) 2015-09-16 2022-05-17 Dfb Soria, Llc Delivery of drug nanoparticles and methods of use thereof
US10918606B2 (en) 2015-09-16 2021-02-16 Dfb Soria, Llc Delivery of drug nanoparticles and methods of use thereof
US10449162B2 (en) 2015-09-16 2019-10-22 Dfb Soria Llc Delivery of drug nanoparticles and methods of use thereof
EP3359085A4 (en) * 2015-10-12 2019-09-18 Toth, Landy CONTROLLED AND PRECISE TREATMENT OF HEARTWOVEN
US11185361B2 (en) 2015-10-12 2021-11-30 Landy Toth Controlled and precise treatment of cardiac tissues
US11191717B2 (en) 2017-03-15 2021-12-07 Dfb Soria, Llc Topical therapy for the treatment of skin malignancies using nanoparticles of taxanes
US10555898B2 (en) 2017-03-15 2020-02-11 Dfb Soria, Llc Topical therapy for the treatment of skin malignancies using nanoparticles of taxanes
US10842736B2 (en) 2017-03-15 2020-11-24 Dfb Soria, Llc Topical therapy for the treatment of skin malignancies using nanoparticles of taxanes
US11633349B2 (en) 2017-03-15 2023-04-25 Dfb Soria, Llc Topical therapy for the treatment of skin malignancies using nanoparticles of taxanes
WO2019040335A1 (en) 2017-08-19 2019-02-28 University Of Rochester MICHELOLID DERIVATIVES, PREPARATION METHODS AND THEIR USE AS ANTICANCER AND ANTI-INFLAMMATORY AGENTS
US11497726B2 (en) 2018-03-16 2022-11-15 Dfb Soria, Ll. Topical therapy for the treatment of cervical intraepithelial neoplasia (CIN) and cervical cancer using nanoparticles of taxanes
US11628466B2 (en) 2018-11-29 2023-04-18 Surmodics, Inc. Apparatus and methods for coating medical devices
US11819590B2 (en) 2019-05-13 2023-11-21 Surmodics, Inc. Apparatus and methods for coating medical devices

Also Published As

Publication number Publication date
KR20080043375A (ko) 2008-05-16
DK0706376T4 (da) 2007-12-10
EP1159975A3 (en) 2002-03-27
PT1159974E (pt) 2007-10-31
EP1155691A3 (en) 2002-05-29
DE69403966T2 (de) 1998-02-05
US20060240113A1 (en) 2006-10-26
EP1155690B1 (en) 2004-09-29
EP0706376A1 (en) 1996-04-17
US20020119202A1 (en) 2002-08-29
RU2304433C2 (ru) 2007-08-20
US20080020063A1 (en) 2008-01-24
ATE407712T1 (de) 2008-09-15
CA2472373C (en) 2009-10-13
ATE537858T1 (de) 2012-01-15
CN100998565A (zh) 2007-07-18
EP2226085A1 (en) 2010-09-08
EP0797988A2 (en) 1997-10-01
US20090074830A1 (en) 2009-03-19
PT2226085E (pt) 2014-03-04
NZ268326A (en) 1997-12-19
DK0797988T3 (da) 2009-05-11
US20110071612A1 (en) 2011-03-24
EP0706376B1 (en) 1997-06-25
EP1159975B1 (en) 2008-09-10
DE69435342D1 (de) 2011-05-05
US20050208137A1 (en) 2005-09-22
US20060127445A1 (en) 2006-06-15
JP4597115B2 (ja) 2010-12-15
RU2001132111A (ru) 2003-07-27
CN1502331A (zh) 2004-06-09
KR100389223B1 (ko) 2003-10-08
US20090036517A1 (en) 2009-02-05
DK1155689T3 (da) 2006-11-20
US20110066251A1 (en) 2011-03-17
DE69435139D1 (de) 2008-10-23
US20050123605A1 (en) 2005-06-09
EP1652539A1 (en) 2006-05-03
US20030003094A1 (en) 2003-01-02
CN100998869A (zh) 2007-07-18
LU92422I2 (en) 2015-01-20
HK1042054B (zh) 2008-11-14
AU7119294A (en) 1995-02-20
DK0706376T5 (da) 2006-05-15
JP2006328086A (ja) 2006-12-07
EP1159974A1 (en) 2001-12-05
EP1159975A2 (en) 2001-12-05
CN1130866A (zh) 1996-09-11
ATE502625T1 (de) 2011-04-15
DK1159974T3 (da) 2007-11-26
ES2267638T3 (es) 2007-03-16
US20080166387A1 (en) 2008-07-10
DE69403966D1 (de) 1997-07-31
CA2167268C (en) 2004-09-28
DK0706376T3 (da) 1997-10-13
EP1155691A2 (en) 2001-11-21
ATE154757T1 (de) 1997-07-15
NZ523799A (en) 2005-03-24
NO324275B1 (no) 2007-09-17
EP0706376B2 (en) 2007-08-08
US20040062810A1 (en) 2004-04-01
KR20090090403A (ko) 2009-08-25
ES2321241T3 (es) 2009-06-03
EP1695698B1 (en) 2011-03-23
DE69435185D1 (de) 2009-03-05
DE69434856T2 (de) 2007-03-01
EP1632259A3 (en) 2006-08-09
EP1155689A2 (en) 2001-11-21
DE69435002D1 (de) 2007-08-30
RU2007111679A (ru) 2008-10-10
DK2226085T3 (da) 2014-02-03
US20130102657A1 (en) 2013-04-25
KR20110049898A (ko) 2011-05-12
CA2472373A1 (en) 1995-02-02
EP1155690A3 (en) 2001-11-28
US20100240742A1 (en) 2010-09-23
EP0797988A3 (en) 2000-11-22
NZ511762A (en) 2003-09-26
JP4476536B2 (ja) 2010-06-09
DE69435341D1 (de) 2011-05-05
AU693797B2 (en) 1998-07-09
CN101185759A (zh) 2008-05-28
US20070003630A1 (en) 2007-01-04
JP2007084572A (ja) 2007-04-05
JP3423317B2 (ja) 2003-07-07
ES2106553T5 (es) 2008-02-16
DE69435141D1 (de) 2008-10-30
JPH09503488A (ja) 1997-04-08
DE69434048T2 (de) 2005-10-06
US20060121117A1 (en) 2006-06-08
CN1138505C (zh) 2004-02-18
EP1652539B1 (en) 2011-03-23
CA2167268A1 (en) 1995-02-02
US20040076672A1 (en) 2004-04-22
PT1155689E (pt) 2007-01-31
EP1155691B1 (en) 2008-09-17
EP1632259A2 (en) 2006-03-08
DE69434048D1 (de) 2004-11-04
ATE367173T1 (de) 2007-08-15
EP1632259B1 (en) 2011-12-21
EP1652539B8 (en) 2011-06-15
CN1704121A (zh) 2005-12-07
NZ533467A (en) 2006-02-24
LU92423I2 (en) 2015-01-20
KR101222904B1 (ko) 2013-01-17
JP4920353B2 (ja) 2012-04-18
US20110118825A1 (en) 2011-05-19
NO20073066L (no) 1996-03-18
CA2472404A1 (en) 1995-02-02
EP1695697A1 (en) 2006-08-30
DE69435002T2 (de) 2008-03-20
EP1155690A2 (en) 2001-11-21
EP1155689A3 (en) 2001-11-28
EP1155689B1 (en) 2006-09-20
NO960226L (no) 1996-03-18
NO960226D0 (no) 1996-01-18
EP0797988B1 (en) 2009-01-14
ES2290074T3 (es) 2008-02-16
CN101185759B (zh) 2011-05-25
JP2002326930A (ja) 2002-11-15
US6544544B2 (en) 2003-04-08
US20070298123A1 (en) 2007-12-27
US7820193B2 (en) 2010-10-26
EP1695697A3 (en) 2007-12-26
EP2226085B1 (en) 2013-11-27
US6506411B2 (en) 2003-01-14
PT797988E (pt) 2009-05-19
EP1159974B1 (en) 2007-07-18
EP1695698A1 (en) 2006-08-30
KR100934111B1 (ko) 2009-12-31
CA2468375A1 (en) 1995-02-02
ES2106553T3 (es) 1997-11-01
EP1946749A1 (en) 2008-07-23
ATE339975T1 (de) 2006-10-15
DE69434856D1 (de) 2006-11-02
HK1042054A1 (en) 2002-08-02
CN1704121B (zh) 2010-08-18
ATE420628T1 (de) 2009-01-15
US20070003629A1 (en) 2007-01-04
ES2449311T3 (es) 2014-03-19
DE69403966T3 (de) 2008-04-17
ATE277649T1 (de) 2004-10-15
US20020164377A1 (en) 2002-11-07
US20100292314A1 (en) 2010-11-18
GR3024833T3 (en) 1998-01-30
NZ329193A (en) 2001-08-31
CN101007173A (zh) 2007-08-01
US8221794B2 (en) 2012-07-17
ATE502664T1 (de) 2011-04-15
DE69434856T4 (de) 2009-09-24
ATE408429T1 (de) 2008-10-15
HK1079715A1 (en) 2006-04-13
KR20030097620A (ko) 2003-12-31
RU2180844C2 (ru) 2002-03-27

Similar Documents

Publication Publication Date Title
AU693797B2 (en) Anti-angiogenic compositions and methods of use
US6846841B2 (en) Anti-angiogenic compositions and methods of use
AU771815B2 (en) Anti-angiogenic compositions and methods of use
AU728873B2 (en) Anti-angiogenic compositions and methods of use
AU2011218716A1 (en) Anti-angiogenic compositions and methods of use
AU2004200646A1 (en) Anti-angiogenic compositions and methods of use

Legal Events

Date Code Title Description
WWE Wipo information: entry into national phase

Ref document number: 94193379.2

Country of ref document: CN

AK Designated states

Kind code of ref document: A1

Designated state(s): AM AT AU BB BG BR BY CA CH CN CZ DE DK ES FI GB GE HU JP KE KG KP KR KZ LK LT LU LV MD MG MN MW NL NO NZ PL PT RO RU SD SE SI SK TJ TT UA US UZ VN

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): KE MW SD AT BE CH DE DK ES FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN ML MR NE SN TD TG

DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
121 Ep: the epo has been informed by wipo that ep was designated in this application
WWE Wipo information: entry into national phase

Ref document number: 2167268

Country of ref document: CA

WWE Wipo information: entry into national phase

Ref document number: 268326

Country of ref document: NZ

WWE Wipo information: entry into national phase

Ref document number: 1994920360

Country of ref document: EP

WWP Wipo information: published in national office

Ref document number: 1994920360

Country of ref document: EP

REG Reference to national code

Ref country code: DE

Ref legal event code: 8642

WWG Wipo information: grant in national office

Ref document number: 1994920360

Country of ref document: EP

ENP Entry into the national phase

Ref document number: 1997 984258

Country of ref document: US

Date of ref document: 19971203

Kind code of ref document: A

WWE Wipo information: entry into national phase

Ref document number: 1020027016338

Country of ref document: KR

WWE Wipo information: entry into national phase

Ref document number: 1020087007363

Country of ref document: KR

WWE Wipo information: entry into national phase

Ref document number: 1020097015869

Country of ref document: KR

WWE Wipo information: entry into national phase

Ref document number: 1020117007294

Country of ref document: KR